In JoVE (1)

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Articles by Hillol K. Das in JoVE

 JoVE Engineering

Bringing the Visible Universe into Focus with Robo-AO

1Caltech Optical Observatories, California Institute of Technology, 2Department of Astronomy, California Institute of Technology, 3Dunlap Institute for Astronomy and Astrophysics, University of Toronto, 4Inter-University Centre for Astronomy & Astrophysics, 5Observatories of the Carnegie Institution for Science, 6Benoziyo Center for Astrophysics, Weizmann Institute of Science

JoVE 50021

Other articles by Hillol K. Das on PubMed

Dose Perturbation Study in a Multichannel Breast Brachytherapy Device

Journal of Contemporary Brachytherapy. Dec, 2011  |  Pubmed ID: 23346131

A study was conducted to determine the dosimetric effects resulting from air pockets and high atomic number (Z) contrast medium within a multichannel breast brachytherapy device.

A Spatial Statistical Approach to Analyze Malaria Situation at Micro Level for Priority Control in Ranchi District, Jharkhand

The Indian Journal of Medical Research. Nov, 2012  |  Pubmed ID: 23287124

Background & objectives: The presence of efficient malaria vectors namely Anopeles culicifacies, An. fluviatilis and An. annularis (Diptera: Culicidae), rapid industrialization causing large influx of population and poor health infrastructure are some of the factors that make malaria an important public health problem in Ranchi, the capital of Jharkhand State, India. A geographical information system (GIS) based retrospective study using spatial statistical tools was initiated in 328 subcentres of 14 primary health centres (PHCs) of the district using malaria epidemiological data of three years (2007-2009) to identify spatial distribution pattern of Plasmodium vivax (Pv) and Plasmodium falciparum (Pf) occurrence, delineation of hot spots and to map directional distribution trend of Pf spread to help formulate evidence-based policy and to prioritize control during 2011. Methods: Spatial statistics tools like Global Moran's I index, Getis-Ord GiFNx01 and Standard Deviational Ellipse were used in GIS domain for analysis. Results: Spatial distribution pattern of Pv occurrence was found random while Pf distribution was significantly clustered. During 2007-2009, the number of subcentres under Pf hot spot category exhibited downward trend while high Pf risk subcentres exhibited upward trend. One consistent Pf hot spot consisting of five subcentres was identified in Silli PHC. During 2009, one Pf hot spot consisting of 20 subcentres and 18 subcentres under high Pf risk category were identified in Angara, Silli, Burmu and Kanke PHCs. A shifting trend in Pf spread was noticed from north-west to western direction from 2008 onwards. Interpretation & conclusions: The study recommended priority control in 20 Pf hot spot and 18 high Pf risk reporting subcentres including five consistent Pf hot spot subcentres in Angara, Silli, Burmu and Kanke PHCs during 2011 to address grave malaria situation in the district in a cost-effective manner.

Characterization of Nasopharyngeal Isolates of Type B Haemophilus Influenzae from Delhi

The Indian Journal of Medical Research. Nov, 2012  |  Pubmed ID: 23287135

Background & objectives: Haemophilus influenzae is an important cause of mortality and morbidity among young children in developing countries. Increasing incidence of antibiotic resistance especially production of extended spectrum beta lactamase (ESBL) has made treatment and management of H. influenzae infection more difficult. Nasopharyngeal H. influenzae isolates are excellent surrogate for determination of antibiotic resistance prevalent among invasive H. influenzae isolates. In this study, we characterized nasopharyngeal H. influenzae isolates obtained from healthy school going children in Delhi. Methods: Nasopharyngeal H. influenzae isolates were collected from healthy school going children and subjected to serotyping, fimbrial typing and antibiogram profiling. ESBL production was recorded using phenotypic as well as molecular methods. Multi locus sequence typing (MLST) of 13 representative nasopharyngeal H. influenzae isolates was performed as per guidelines. Results: A significant proportion (26 of 80, 32.5%) of nasopharyngeal isolates of H. influenzae were identified as serotype b. Fimbrial gene (hifA) was detected in 23 (28.75%) isolates. Resistance against commonly prescribed antibiotics (Amp, Tet, Chloro, Septran, Cephalexin) were observed to be high among the nasopharyngeal commensal H. influenzae. Extended spectrum beta lactamase (ESBL) production was observed in a five (6.25%) isolates by both double disk diffusion and molecular typing. MLST identified several novel alleles as well as novel sequence types. Interpretation & conclusions: Our findings showed high resistance against common antibiotics and detection of ESBL in nasopharyngeal H. influenzae isolates collected from normal healthy school going children in Delhi. Detection of H. influenzae type b capsular gene and the presence of fimbrial gene (hif A) suggest virulence potential of these isolates. Discovery of novel alleles and presence of new sequence types (STs) among nasopharyngeal H. influenzae isolates may suggest wider genetic diversity.

Dementia: Indian Scenario

Neurology India. Nov-Dec, 2012  |  Pubmed ID: 23287325

As per the estimates of the World Health Organization, aging population is increasing in developing countries and dementia is going to become epidemic among elderly in the coming decades. This demands early action to prevent the disease and treatment of the affected persons, which is poorly existent in middle- and low-income countries. The need of the hour to tackle dementia in India is to estimate disease burden in the community, search for risk and protective factors of dementia, and undertake measures to provide social benefits to the sufferers and those who are at risk. Raising awareness among the public and general physicians is an important task ahead. In India, there is lack of good longitudinal studies which can provide true trend of the disease and determine risk factors, paucity of basic and clinical researches on dementia, poor awareness, and inadequate availability of social benefit. India, being a country of diverse ethnicity and cultures, has great advantages to carry out genetic epidemiological study. The information may be useful for undertaking remedial measure. This article will highlight the existing state of the above medical and social issues and deficiencies, so that the stakeholders can make adequate preparation to provide relief to the dementia patients and those who are at risk. It is expected that the medical and scientific community will draw attention to the medical problem with the help of governmental and non-governmental agencies, and the political leadership will be motivated to undertake the issue of providing socioeconomic benefit to families of the victims.

A Rare Case of Intussusception Associated with Metastasize Small Cell Carcinoma of Lung

Acta Medica Iranica. Nov, 2012  |  Pubmed ID: 23292632

Intussusception is common cause of bowel obstruction in the paediatric age group compared to the elderly population. Many times, The diagnosis may be difficult because of asymptomatic nature of this bowel disorder. We hereby describe the case of a 75-year-old male who presented with lethargy, weakness, loss of movement in the joints and was found to be anemic. The haemoglobin level was low so he was transfused with packed cells. On gastrointestinal (GI) endoscopy, upper GI bleed was observed. A mass was observed beyond ampulla at the 2nd and 3rd part of the duodenal junction. Computerized tomography (CT) scan also showed a mass at the head of pancreas and the lesion at the left lung. In view of persistent bleed, 'Whipple's procedure' was performed. Histopathological examination showed small cell carcinoma of the lungs with metastasis to the pancreas and the jejunum. We here discuss the case of intussusception with intestinal metastasis which presented with gastrointestinal bleeding.

Burden of Hospitalized Pediatric Morbidity and Utilization of Beds in a Tertiary Care Hospital of Kolkata, India

Indian Journal of Community Medicine : Official Publication of Indian Association of Preventive & Social Medicine. Oct, 2012  |  Pubmed ID: 23293440

Childhood morbidity consumes a substantial portion of health care resources in terms of hospital bed utilization, and overload in hospital ward remains a major concern in many countries, including India. A possible way to minimize the problem of scarcities of bed is to analyze the pattern of bed utilization by causes and plan services accordingly.

Why Are We Still in the 1950s Regarding Management of Cancer of Uterine Cervix ?

Journal of Medical Physics / Association of Medical Physicists of India. Oct, 2012  |  Pubmed ID: 23293447

Comparative Study to Evaluate Shear Bond Strength of RMGIC to Composite Resin Using Different Adhesive Systems

Contemporary Clinical Dentistry. Jul, 2012  |  Pubmed ID: 23293476

The aim of the study is to compare and evaluate the role of new dental adhesives to bond composite to the resinmodified glass inomer cement (RMGIC).

Adjuvant and Neoadjuvant Therapy for Gastric Cancer: Taking Stock of the Options

Gastrointestinal Cancer Research : GCR. Nov, 2012  |  Pubmed ID: 23293702

An Ergonomics Study on the Prevalence of Musculoskeletal Disorders Among Indian Bus Conductors

International Journal of Occupational Safety and Ergonomics : JOSE. 2012  |  Pubmed ID: 23294656

This study was undertaken among 100 randomly selected bus conductors from 2 routes. A questionnaire study based on the modified Nordic musculoskeletal questionnaire, assessment of physical and physiological parameters, analysis of working postures and a detailed work study were performed. The analysis revealed that conductors had a work schedule of 16-18 h each day; the duration of work could vary from 15 to 20 days at a stretch. Discomfort leading to musculoskeletal disorders mainly affecting the leg (93.3%), knee (83.3%), shoulder (80%) and back areas (56.7%) had the highest 12-month prevalence rates and increased day by day. The conductors also suffered from extreme physiological stress due to prolonged working hours in hazardous standing posture conditions, excessive work pressure and minimum rest between trips. Consequently, all those factors affected their health and work performance.

Assessment of Ergonomic and Occupational Health-related Problems Among Female Prawn Seed Collectors of Sunderbans, West Bengal, India

International Journal of Occupational Safety and Ergonomics : JOSE. 2012  |  Pubmed ID: 23294657

Sixty female prawn seed collectors and 60 female control subjects from Sajenakhali and Sandeshkhali blocks of Sunderbans, West Bengal, India, were randomly selected to evaluate and compare musculoskeletal disorders and physiological stress. The control group was engaged in domestic work involving minimum hand intensive activities. The modified Nordic musculoskeletal questionnaire and rapid entire body assessment were used. Most subjects suffered from discomfort in different body parts, especially in the lower back (98%), knees (88%), shoulders (75%), ankles (70%) and feet (67%). This study reveals that female prawn seed collectors suffer from significant physiological load and extreme physiological stress due to prolonged working hours in a standing posture and excessive work pressure. Consequently, all these factors affect female prawn seed collectors' health and work performance.

Resection and Primary Anastomosis with Modified Blow-Hole Colostomy or Hartmann's Procedure. Which Method Should Be Performed for Gangrenous Sigmoid Volvulus?

Chirurgia (Bucharest, Romania : 1990). Nov-Dec, 2012  |  Pubmed ID: 23294953

Aim: To evaluate the efficacy of Hartmann's procedure and RPA with modified blow-hole colostomy for gangrenous sigmoid volvulus. Methods: Sixty-one patients operated on between January 2004 to September 2010 were reviewed retrospectively. The demographic data of the patients,clinical features, type of surgical procedure performed, postoperative complications, mortality and duration of hospital stay (DHS) after surgery were reviewed. Results: The mean hospital stay, wound infection and mortality did not differ significantly between the groups. Superficial wound infection rate was higher in group A (32% vs15%). Development of leaks secondary to stoma closure was not observed in any patient. During hospitalisation period; the postoperative complications were wound infection in four patients, intraabdominal abscess in two, evisceration and wound dehiscence in two, arrhythmia in six, pneumonia in eight.Medical and surgical complication rates of the groups were not different (p>0.05). When compared, the durations of intensive care unit (ICU) stay were not statistically different (p>0.05), but mean duration of hospital stay (DHS) was longer in group A than group B (p less than 0.05). Conclusion: Sigmoidectomy should be the basic principle in the management of sigmoid volvulus.RPA with modified blow - hole colostomy provides satisfactory results. It is easy to perform in patients with sigmoid volvulus. RPA with modified blow - hole colostomy can be performed safely in selected patients without increasing morbidity and DHS.

Babesia Bigemina Infection in Yak (Poephagus Grunniens L.): Molecular Detection and Characterization

Veterinary Parasitology. Dec, 2012  |  Pubmed ID: 23298564

Yaks contribute significantly in the Himalayan high land economy. Specific information on prevalence of babesiosis in yaks is lacking. A fast and reliable PCR assay targeting Babesia bigemina small subunit ribosomal RNA sequence (SS rRNA) was laboratory standardized for molecular detection of B. bigemina in yaks. Restriction digestion of the PCR amplified 675bp target sequence with Vsp I confirmed the prevalent species of Babesia as B. bigemina. Nucleotide sequencing and phylogenetic analysis of PCR amplified 675bp SS rRNA sequence revealed a close genetic relationship with other bovine isolates of B. bigemina. A PCR based survey involving 94 blood samples of yak from the National Research Centre on Yak, Dirang, Arunachal Pradesh detected infection in 5.32% of yak blood samples, which was significantly higher in comparison to microscope based detection of infection in 2.13% blood smears. This is the first report on sensitive PCR based detection of B. bigemina infection in yaks and PCR-RFLP and nucleotide sequence analysis based molecular characterization of the B. bigemina isolated from yaks.

Evaluation of Clinical Features Scoring System As Screening Tool for Influenza A (H1N1) in Epidemic Situations

Journal of Postgraduate Medicine. Oct, 2012  |  Pubmed ID: 23298921

Background: Influenza A (H1N1) hit the headlines in recent times and created mass hysteria and general panic. The high cost and non-availability of diagnostic laboratory tests for swine flu, especially in the developing countries underlines the need of having a cheaper, easily available, yet reasonably accurate screening test. Aims: This study was carried out to develop a clinical feature-based scoring system (CFSS) for influenza A (H1N1) and to evaluate its suitability as a screening tool when large numbers of influenza-like illness cases are suspect. Settings and Design: Clinical-record based study, carried out retrospectively in post-pandemic period on subject's case-sheets who had been quarantined at IG International Airport's quarantine center at Delhi. Materials and Methods: Clinical scoring of each suspected case was done by studying their case record sheet and compared with the results of RT-PCR. RT-PCR was used to confirm the diagnosis (Gold Standard). Statistical Analysis: We calculated sensitivity, specificity, positive and negative predictive values of the clinical feature-based scoring system (the proposed new screening tool) at different cut-off values. The most discriminant cut-off value was determined by plotting the ROC curve. Results: Of the 638 suspected cases, 127 (20%) were confirmed to have H1N1 by RT-PCR examination. On the basis of ROC, the most discriminant clinical feature score for diagnosing Influenza A was found to be 7, which yielded sensitivity, specificity, positive, and negative predictive values of 86%, 88%, 64%, and 96%, respectively. Conclusion: The clinical features scoring system (CFSS) can be used as a valid and cost-effective tool for screening swine flu (influenza A (H1N1)) cases from large number of influenza-like illness suspects.

A Patient of Chronic Myelogenous Leukemia Developing Painful Rash on Feet

Journal of Postgraduate Medicine. Oct, 2012  |  Pubmed ID: 23298941

Imipramine Is an Orally Active Drug Against Both Antimony Sensitive and Resistant Leishmania Donovani Clinical Isolates in Experimental Infection

PLoS Neglected Tropical Diseases. Dec, 2012  |  Pubmed ID: 23301108

In an endeavor to find an orally active and affordable antileishmanial drug, we tested the efficacy of a cationic amphiphilic drug, imipramine, commonly used for the treatment of depression in humans. The only available orally active antileishmanial drug is miltefosine with long half life and teratogenic potential limits patient compliance. Thus there is a genuine need for an orally active antileishmanial drug. Previously it was shown that imipramine, a tricyclic antidepressant alters the protonmotive force in promastigotes, but its in vivo efficacy was not reported.

Effect of Piper Sarmentosum Extract on the Cardiovascular System of Diabetic Sprague-Dawley Rats: Electron Microscopic Study

Evidence-based Complementary and Alternative Medicine : ECAM. 2012  |  Pubmed ID: 23304208

Although Piper sarmentosum (PS) is known to possess the antidiabetic properties, its efficacy towards diabetic cardiovascular tissues is still obscured. The present study aimed to observe the electron microscopic changes on the cardiac tissue and proximal aorta of experimental rats treated with PS extract. Thirty-two male Sprague-Dawley rats were divided into four groups: untreated control group (C), PS-treated control group (CTx), untreated diabetic group (D), and PS-treated diabetic group (DTx). Intramuscular injection of streptozotocin (STZ, 50 mg/kg body weight) was given to induce diabetes. Following 28 days of diabetes induction, PS extract (0.125 g/kg body weight) was administered orally for 28 days. Body weight, fasting blood glucose, and urine glucose levels were measured at 4-week interval. At the end of the study, cardiac tissues and the aorta were viewed under transmission electron microscope (TEM). DTx group showed increase in body weight and decrease in fasting blood glucose and urine glucose level compared to the D group. Under TEM study, DTx group showed lesser ultrastructural degenerative changes in the cardiac tissues and the proximal aorta compared to the D group. The results indicate that PS restores ultrastructural integrity in the diabetic cardiovascular tissues.

Sim•TwentyFive: An Interactive Visualization System for Data-Driven Decision Support

AMIA ... Annual Symposium Proceedings / AMIA Symposium. AMIA Symposium. 2012  |  Pubmed ID: 23304364

Clinicians at the bedside are increasingly overwhelmed by an inundation of information and must rely largely on pattern recognition and professional experience to comprehend complex clinical data and treat their patients in a timely manner. Traditional decision support systems are based on rules and predictive models and often fail to take advantage of increasingly large digital clinical data stores available in real-time. We propose an alternative approach to delivering data-driven decision support based on an interactive system for exploring and visualizing a context of physiologically similar patients from a database. Here we present Sim•TwentyFive, a highly flexible, responsive, intuitive prototype with a comprehensive set of interaction techniques that effectively reduces the cognitive burden of querying, exploring, analyzing and comparing similar past patient episodes. Quantitative performance tests and anonymous summative evaluations from PICU physicians indicated that Sim•TwentyFive is an efficient, intuitive and clinically-useful tool.

Oncoshare: Lessons Learned from Building an Integrated Multi-institutional Database for Comparative Effectiveness Research

AMIA ... Annual Symposium Proceedings / AMIA Symposium. AMIA Symposium. 2012  |  Pubmed ID: 23304372

Comparative effectiveness research (CER) using observational data requires informatics methods for the extraction, standardization, sharing, and integration of data derived from a variety of electronic sources. In the Oncoshare project, we have developed such methods as part of a collaborative multi-institutional CER study of patterns, predictors, and outcome of breast cancer care. In this paper, we present an evaluation of the approaches we undertook and the lessons we learned in building and validating the Oncoshare data resource. Specifically, we determined that 1) the state or regional cancer registry makes the most efficient starting point for determining inclusion of subjects; 2) the data dictionary should be based on existing registry standards, such as Surveillance, Epidemiology and End Results (SEER), when applicable; 3) the Social Security Administration Death Master File (SSA DMF), rather than clinical resources, provides standardized ascertainment of mortality outcomes; and 4) CER database development efforts, despite the immediate availability of electronic data, may take as long as two years to produce validated, reliable data for research. Through our efforts using these methods, Oncoshare integrates complex, longitudinal data from multiple electronic medical records and registries and provides a rich, validated resource for research on oncology care.

Foot Care Strategy for the Newly Diagnosed DM Type 2 Patients with Low Educational and Socio-economic Background: A Step Towards Future

La Clinica Terapeutica. Nov, 2012  |  Pubmed ID: 23306740

Background and Aims. Diabetic foot ulcer is one of the major health problems that accounts for increased morbidity among the diabetic patients. Having good knowledge, good attitude and practice of managing the foot prevents the impending chronic co-morbidities of the disease. Materials and Methods. This cross-sectional study was performed to assess the knowledge, attitude and practice on foot care among the newly diagnosed diabetic type 2 patients with low education and socio economic background. This study was conducted in one of the out patient clinics in a tertiary hospital. A set of questionnaire adopted from The Michigan Diabetes Research and Training Center (MDRTC), was used to assess 109 respondents based on their knowledge of diabetes mellitus, practice and attitude towards the condition and care of the feet. Results. The overall finding on knowledge, practice and attitude had shown unsatisfactory result. There was no relationship between the knowledge, practice and attitude with care of the feet. Only 20 (18.3%) respondents had a high score on knowledge, 31 (28.4%) had practiced good habits and 5 (4.6%) showed positive attitude towards care of the feet. However, there was significant finding on the level of education and the knowledge of foot care (p=0.01); Conclusion. Strategies should be developed to overcome the longterm complications. As for the Muslim patients, ablution, the ritual practice of washing and cleaning both feet prior to the prayers may be a possible means of checking the feet for any diabetic foot complication. Clin Ter 2012; 163(6):473-478.

Spinal Arteriovenous Malformation Presenting with Prolapsed Intervertebral Disc: a Diagnostic Dilemma

La Clinica Terapeutica. Nov, 2012  |  Pubmed ID: 23306743

The availability of multiple investigating modalities should be utilized to arrive at the correct diagnosis of the spinal arteriovenous malformation (AVM). We hereby report the case of a 21-year-old, obese female, who presented with paraplegia and impaired bowel control two years after an episode of the fall. The Magnetic Resonance Imaging (MRI) of her spine not only revealed disc prolapse at T11-T12, but also tortuous dilated spinal veins and cord oedema. A diagnosis of a spinal arterio-venous fistula was confirmed after a spinal angiogram. The dilemma of treating the right pathology for the clinical signs and symptoms are being discussed. Clin Ter 2012; 163(6):491-493.

An Interesting Case of Isolated Pancreatic Teratoma: Lessons to Learn

La Clinica Terapeutica. Nov, 2012  |  Pubmed ID: 23306744

Mature cystic teratomas of the pancreas are extremely rare tumours encountered in day-to-day clinical practice. Only few cases have been reported to date involving all age groups. The management, diagnosis and evaluation of this tumor are questionable, with definitive diagnosis taking place intra-operatively. We hereby report the case in a 30 year-old-male who presented with newly diagnosed diabetes mellitus and during the follow up he was noted to have elevated liver enzymes clinically, he was asymptomatic. The computerized tomography revealed a retropancreatic mass and pushing the mesenteric veins anteriorly. The mass was hypodense in nature and there was presence of calcification. Although the patient was asymptomatic, the decision for resecting the mass was made in view of the size and possibility of malignancy. In conclusion, considering the size and approximity of the mass to the pancreas, Whipple procedure's is the most appropriate approach although the histological diagnosis has not been established preoperatively. Clin Ter 2012; 163(6):495-497.

Absence of the Isthmus of the Thyroid Gland: Anatomical and Clinical Considerations

La Clinica Terapeutica. Nov, 2012  |  Pubmed ID: 23306746

The right and left lobes of the thyroid gland are connected by an isthmus. The isthmus lies at the level of the second and third tracheal rings. Occasionaly, the isthmus may be absent. We hereby, report the absence of isthmus in a 52-year-old male cadaver of unknown origin. Both the right and left lobes were normal but they were separated. Both the right and left lobes of the thyroid gland measured 4.3 cm vertically. The separation distance between right and left glands was noted at the upper, middle and lower parts. The upper end of medial border of both lobes were separated by a distance of 1 cm while the separation distance was 0.7 cm and 1.5 cm at the middle and lower parts, respectively. The anatomical and clinical significance of absence of isthmus is important for medical personnel and the surgeons operating on the thyroid gland. The present case report is a an attempt to highlight such. Clin Ter 2012; 163(6):503-504.

Use Piper Sarmentosum As an Effective Antidiabetic Supplement in South East Asia: a Review

La Clinica Terapeutica. Nov, 2012  |  Pubmed ID: 23306747

Herbs with antidiabetic activity have a potential role to play. Herbal medicines have been widely used in South East Asia because of lesser side effects and cost effectiveness. The main aim of this review article was to disseminate important information regarding the use of herbal products in oxidative stress involved in diseases like diabetes mellitus. The article highlights some of the traditional medicinal plants which have been widely used in South East Asia with special emphasis on Piper sarmentosum. Piper sarmentosum have been reported to possess varying degree of hypoglycemic, antidiabetic and other additional properties. The antioxidant properties of the herbs may be effective in controlling the oxidative damage produced during diabetes mellitus. The review article highlights the positive role of traditional herbs towards diabetes mellitus and also describes its complications. Clin Ter 2012; 163(6):505-510.

Green Pigmented Teeth

Indian Pediatrics. Dec, 2012  |  Pubmed ID: 23315123

Molecular Sexing of Threatened Gyps Vultures: an Important Strategy for Conservation Breeding and Ecological Studies

SpringerPlus. Dec, 2012  |  Pubmed ID: 23316450

During the last two decades populations of three resident species of Gyps vulture have declined dramatically and are now threatened with extinction in South Asia. Sex identification of vultures is of key importance for the purpose of conservation breeding as it is desirable to have an equal sex ratio in these monogamous species which are housed together in large colony aviaries. Because vultures are monomorphic, with no differences in external morphology or plumage colour between the sexes, other methods are required for sex identification. Molecular methods for sex identification in birds rely on allelic length or nucleotide sequence discrimination of the chromohelicase-DNA binding (CHD) gene located on male and female chromosomes ZZ and ZW, respectively. We characterized the partial sequences of CHD alleles from Gyps indicus, Gyps bengalensis, Gyps himalayensis and Aegypius monachus and analysed the applicability of five molecular methods of sex identification of 46 individual vultures including 26 known-sex G. bengalensis and G. indicus. The results revealed that W-specific PCR in combination with ZW-common PCR is a quick, accurate and simple method, and is ideal for sex identification of vultures. The method is also suitable to augment ecological studies for identifying sex of these endangered birds during necropsy examinations especially when gonads are not apparent, possibly due to regression during non-breeding seasons.

Role of Nuclear Factor-κB in Female Breast Cancer: A Study in Indian Patients

Asian Pacific Journal of Cancer Prevention : APJCP. 2012  |  Pubmed ID: 23317209

Introduction: The nuclear factor κB (NF-κB) is a super family of transcription factors which plays important roles in development and progression of cancer. The present investigation concerns NF-κB /p65 activity in human breast cancers with overexpression of ER, PR, HER-2/neu, as well as the significance of p65 expression with regard to menopausal status, stage, grade, tumor size, nodal status, and NPI of invasive ductal carcinomas in Eastern India. Materials and Methods: In this hospital based study 57 breast cancer patients attending a Breast Clinic of a reputed institute of Eastern India were assessed for p65 protein expression in breast tumor tissue samples by Western blotting. ER, PR and HER-2/neu expression was determined by immunohistochemistry. Results: NF-κB/p65 was significantly associated with advanced stage, large tumor size (≥5 cm), high grade, negative ER, negative PR, and positive HER-2/neu. High NF-κB/p65 expression was more frequent in patients with a high NPI (NPI ≥ 5.4, 84.6%) compared with low NPI (<5.4, 44.4%) and this association was statistically significant (p = 0.002). Conclusion: NF-κB/p65 overexpression was associated with advanced stage, large tumor size, high grade, and high NPI which are poor prognostic factors linked to enhanced aggressiveness of the disease. NF-κB/p65 expression implies aggressive biological behavior of breast cancer and this study validates significant association of NF-κB /p65 overexpression with negative estrogen and progesterone receptor status and overexpression of HER-2/neu oncoprotein. In our good clinical practice, patients with NF-κB positive tumors need to be treated aggressively.

Nondiabetic Kidney Disease in Type 2 Diabetic Patients: A Single Center Experience

Indian Journal of Nephrology. Sep, 2012  |  Pubmed ID: 23326046

Nondiabetic renal disease (NDRD) is seen as a cause of proteinuria and renal failure in type 2 diabetes mellitus (DM). The clinical differences between NDRD and diabetic glomerulosclerosis (DGS) are not clear. This study was done to find the spectrum of NDRD in type 2 DM patients and differences in clinical profile between NDRD and DGS patients. Data of patients with type 2 DM who underwent renal biopsy in this institute from 1990 to 2008 were analyzed retrospectively. Patients were categorized as isolated NDRD, NDRD with DGS, and isolated DGS. A total of 75 patients were included. Mean age was 45 ± 10.2 years, male to female ratio was 3.1 : 1, median duration of DM was 12 months (range, 1 year-15 years), proteinuria was 4.2 ± 3.4 g/day, and serum creatinine was 4.3 ± 3.9 mg/dl. Hypertension was observed in 63 (84%) cases and microscopic hematuria in 24 (32%) cases. Nephrotic syndrome (38.7%) was the commonest clinical presentation. Forty-eight (64%) cases had NDRD and 27 (36%) had DGS. The commonest NDRD was minimal change disease (12.5%). Three (6.3%) patients had lupus nephritis. Tubulointerstitial nephritis has been observed in 10.4% patients. No significant differences between NDRD and DGS patients were found except hypertension which was significantly high in the DGS group. Acute kidney injury and nephritic syndrome were not observed in the DGS group. In conclusion, the incidence of biopsy-proven NDRD in type 2 DM in this study was high. Kidney biopsy aided in the detection of NDRD in clinically suspected patients.

Comparison of the Effectiveness and Safety of Cefpodoxime and Ciprofloxacin in Acute Exacerbation of Chronic Suppurative Otitis Media: A Randomized, Open-labeled, Phase IV Clinical Trial

Journal of Pharmacology & Pharmacotherapeutics. Oct, 2012  |  Pubmed ID: 23326103

To compare the effectiveness and safety of cefpodoxime and ciprofloxacin for the treatment of mild to moderate cases of acute exacerbation of chronic suppurative otitis media (AECSOM).

Spontaneous Intracranial Hypotension in a Patient with Marfan's Syndrome Treated with Epidural Blood Patch--a Case Report

Middle East Journal of Anesthesiology. Feb, 2012  |  Pubmed ID: 23327040

Spontaneous intracranial hypotension (SIH) is a well-defined clinical entity that is frequently misdiagnosed. We are reporting a case of 38 years old male who presented with severe headache and an episode of generalized tonic-clonic seizure. He was managed successfully with an epidural blood patch. Understanding of the characteristics, symptomatology, evaluation, treatment options, and prognosis is discussed.

Foot-and-mouth Disease Virus Serotypes Detected in Tanzania from 2003 to 2010: Conjectured Status and Future Prospects

The Onderstepoort Journal of Veterinary Research. 2012  |  Pubmed ID: 23327382

This study was conducted to investigate the presence of foot-and-mouth disease virus (FMDV) in different geographic locations of Tanzania. Epithelial tissues and fluids (n = 364) were collected from cattle exhibiting oral and foot vesicular lesions suggestive of FMD and submitted for routine FMD diagnosis. The analysis of these samples collected during the period of 2002 and 2010 was performed by serotype-specific antigen capture ELISA to determine the presence of FMDV. The results of this study indicated that 167 out of 364 (46.1%) of the samples contained FMDV antigen. Of the 167 positive samples, 37 (28.4%) were type O, 7 (4.1%) type A, 45 (21.9%) SAT 1 and 79 (45.6%) SAT 2. Two FMDV serotypes (O and SAT 2) were widely distributed throughout Tanzania whilst SAT 1 and A types were only found in the Eastern zone. Our findings suggest that serotypes A, O, SAT 1 and SAT 2 prevail in Tanzania and are associated with the recent FMD outbreaks. The lack of comprehensive animal movement records and inconsistent vaccination programmes make it difficult to determine the exact source of FMD outbreaks or to trace the transmission of the disease over time. Therefore, further collection and analysis of samples from domestic and wild animals are being undertaken to investigate the genetic and antigenic characteristics of the circulating strains, so that a rational method to control FMD in Tanzania and the neighbouring countries can be recommended.

Durable Complete Remission of a Brainstem Glioma Treated with a Combination of Bevacizumab and Cetuximab

Case Reports in Oncology. Sep, 2012  |  Pubmed ID: 23341811

Treatment of a relapsed glioma is a clinical challenge nowadays. New active treatments are required to treat these difficult diseases. Here we present a durable complete remission of a relapsed glioblastoma that has achieved a complete radiologic response with the combination of cetuximab and bevacizumab, in a third-line setting, that has offered a progression-free survival of 20 months. We consider here both potential mechanisms for the explanation of this result. First, the potential target of the cancer stem cells (CSCs) with these two antibodies, and second, the potential recruitment of the immune system to directly pursue the CSCs.

Effect of Various Concentrations of Sodium Hypochlorite on Primary Dentin: an in Vitro Scanning Electron Microscopic Study

The Journal of Clinical Pediatric Dentistry. 2012  |  Pubmed ID: 23342565

Sodium hypochlorite solutions have been evaluated for their effects in bonding procedures as they are found to deplete or remove the organic portion of the dentin, particularly the collagen fibrils. The aim of this in vitro study was to assess and compare the efficacies of 1%, 2.5%, 5% and 10% NaOCl at 30, 60 and 120s on etched primary dentin.

HIV-1 Escape From RNAi Antivirals: Yet Another Houdini Action?

Molecular Therapy. Nucleic Acids. 2012  |  Pubmed ID: 23344078

Dose Correction in Lung for HDR Breast Brachytherapy

Journal of Contemporary Brachytherapy. Jun, 2012  |  Pubmed ID: 23349652

To evaluate the dosimetric impact of lung tissue in Ir-192 APBI.

Homocysteine in Occlusive Vascular Disease: a Risk Marker or Risk Factor

Indian Journal of Biochemistry & Biophysics. Dec, 2012  |  Pubmed ID: 23350275

Homocysteine has emerged as a significant marker for occlusive vascular disease, but there has been some debate as to whether it is just an association (risk marker) or actually a causative factor (risk factor). To elucidate this, a retrospective statistical analysis was done of data generated in the course of our study on homocysteine and vascular disease. Homocysteine, lipid profile components and lipoprotein(a) were estimated in fasting blood samples drawn from 252 controls and 536 patients of occlusive vascular disease. The data were analyzed by SPSS version 17. Mean homocysteine levels were significantly higher (p < 0.001) in all patients categories, as compared to controls. In fact, homocysteine level was the most significant biochemical risk factor for vascular disease. The odds ratios due to hyperhomocysteinemia varied from 3.170-4.153. When the cut-off was increased by 5 micromol/L, the odds ratio became almost three-fold. The prevalence of hyperhomocysteinemia increased by approximately equal to 20%, when the cut-off was reduced by 5 micromol/L. Statistical analysis of our data revealed that homocysteine conformed to Hill's criteria of causation. Moreover, hyperhomocysteinemia was treatable by the administration of B-vitamins, even if the cause was genetic. Hence morbidity due to vascular disease could be reduced by identification and treatment of hyperhomocysteinemia.

PKI 166 Induced Redox Signalling and Apoptosis Through Activation of P53, MAP Kinase and Caspase Pathway in Epidermoid Carcinoma

Journal of Experimental Therapeutics & Oncology. 2012  |  Pubmed ID: 23350354

Cellular redox changes have emerged as a pivotal and proximal event in cancer. PKI 166 is used to determine the effects of redox sensitive inhibition of EGFR, metastasis and apoptosis in epidermoid carcinoma. Cytotoxicity study of PKI 166 (IC50 1.0 microM) treated A431 cells were performed by MTT assay for 48 and 72 hrs. Morphological analysis of PKI 166 treated A431 cells for 48 hrs. revealed the cell shrinkage, loss of filopodia and lamellipodia by phase contrast and SEM images in dose dependent manner. It has cytotoxic effects through inhibiting cellular proliferation, leads to the induction of apoptosis, as increased fraction of sub-G1 phase of the cell cycle, chromatin condensation and DNA ladder. It inhibited cyclin-D1 and cyclin-E expression and induced p53, p21 expression in dose dependent manner. Consequently, an imbalance of Bax/Bcl-2 ratio triggered caspase cascade and subsequent cleavage of PARP, thereby shifting the balance in favour of apoptosis. PKI 166 treatment actively stimulated reactive oxygen species (ROS) and mitochondrial membrane depolarization. It inhibited some metastatic properties of A431 cells supressing colony formation by soft agar assay and inhibition of MMP 9 activity by gelatin zymography and western blot analysis. PKI 166 inhibited growth factor induced phosphorylation of EGFR, Akt, MAPK, JNK and colony formation in A431 cells. Thus the inhibition of proliferation was associated with redox regulation of the caspase cascade, EGFR, Akt/PI3K, MAPK/ ERK and JNK pathway. On the other hand, increased antioxidant activity leads to decreased ROS generation inhibit the anti-proliferative and apoptotic properties of PKI 166 in A431 cells. These observations indicated PKI 166 induced redox signalling dependent inhibition of cell proliferation, metastatic properties and induction of apoptotic potential in epidermoid carcinoma.

Non-hazardous Anticancerous and Antibacterial Colloidal 'green' Silver Nanoparticles

Colloids and Surfaces. B, Biointerfaces. Dec, 2012  |  Pubmed ID: 23352940

Poly(ethylene glycol) stabilized colloidal silver nanoparticles were prepared using the reductive potency of the aqueous extract of Thuja occidentalis leaves under ambient conditions. The nanoparticles were well dispersed within a narrow size spectrum (7-14nm) and displayed characteristic surface plasmon resonance peak at around 420nm and Bragg's reflection planes of fcc structure. MTT assay revealed the dose-dependent cytocompatibility and toxicity of the nanoparticles with the L929 normal cell line. On the other hand, the antiproliferative action of the nanoparticles was evaluated on HeLa cell (cancerous cells) line. Fluorescence and phase contrast microscopic imaging indicated the appearance of multinucleate stages with aggregation and nuclear membrane disruption of the HeLa cells post treatment with the nanoparticles. The interaction at the prokaryotic level was also assessed via differential antibacterial efficacy against Staphylococcus aureus (MTCC 3160) and Escherichia coli (MTCC 40). Under these perspectives, it is also necessary to observe the environmental impact of the prepared silver nanoparticles. Hence, the dose dependent toxicity of silver nanoparticles was evaluated upon the earthworm species Eisenia fetida. Neither the survival nor the reproduction was affected by the addition of silver nanoparticles up to 1000ppm. Thus these 'green' silver nanoparticles have promising potential as future materials.

Ocular Morbidity Among Children at a Tertiary Eye Care Hospital in Kolkata, West Bengal

Indian Journal of Public Health. Oct-Dec, 2012  |  Pubmed ID: 23354141

Eye diseases in childhood are important causes of medical consultation and it affects learning ability, adjustment in school and personality. To determine the pattern of ocular morbidity a cross-sectional observational study was conducted among 714 children, attending Ophthalmology department at a tertiary eye care center in Kolkata, West Bengal. All the children less than 15 years of age, attending in Unit II outpatient department were selected by complete enumeration method for duration of one year (January-December 2010). Distribution of association was analyzed by Chi-square test and difference between two proportions was calculated by z test for proportions. The common ocular morbidity were refractive errors (23.67%) followed by allergic conjunctivitis (17.23%), infection of the eye and adnexa (15.13%), ocular trauma (12.74%), and congenital eye diseases (13.59%). Majority of ocular morbidity is treatable and need early attention through eye screening cum intervention program beginning right from the childhood.

Apigenin-induced Apoptosis in A375 and A549 Cells Through Selective Action and Dysfunction of Mitochondria

Experimental Biology and Medicine (Maywood, N.J.). Dec, 2012  |  Pubmed ID: 23354402

We isolated apigenin (5,7,4'-trihydroxy flavone) from ethanolic extract of Lycopodium clavatum (LC) used as a homeopathic mother tincture for treatment of various diseases. We assessed the anticancer potentials of the compound using human malignant melanoma cell line A375 and a lung carcinoma cell line A549 and focussed on its putative molecular mechanism of action on apoptosis induction. We examined the cytotoxicity of apigenin in both cancer cells and normal peripheral blood mononuclear cells (PBMC). A375 cells were more prone to apigenin-induced apoptosis, as compared with A549 cells after 24 h of treatment, while PBMC showed little or no cytotoxicity to apigenin. We also evaluated the effects of apigenin on interaction with DNA by comparative analysis of circular dichroism spectral data and melting temperature profiles (Tm) of calf thymus DNA (CT-DNA) treated with or without apigenin. Reactive oxygen species (ROS) accumulation in mitochondria, super-oxide dismutase and total thiol group (GSH) activities were also analyzed. The apoptotic process involved mitochondrial pathway associated with apigenin-DNA interaction, DNA fragmentation, ROS accumulation, cytochrome c (cyt c) release and mitochondrial transmembrane potential depolarization, Bax, caspase 3, 9, PARP, up-regulation, Bcl-2 down-regulation and down-regulation of cyt c in the mitochondrial fraction. Results of mitochondrial inner membrane swelling measurements, intracellular ADP/ATP ratio and ATPase activity showed that in A549 cells, apigenin did not appear to directly target the mitochondrial oxidative phosphorylation system but rather acted at an upstream step to activate the mitochondrial apoptotic pathway. However, apigenin could directly target and impair mitochondrial function in A375 cells by breaking down their oxidative phosphorylation system. Collectively, these results suggest that apigenin exhibits anticancer potential in A375 and A549 cells that may be mediated through DNA interaction, damage and mitochondrial dysfunction either by direct or indirect action on mitochondrial oxidative phosphorylation system.

Use of Fasciocutaneous Flop for Open-type III B Tibial Fractures--clinical Experience and Analysis

Journal of the Indian Medical Association. May, 2012  |  Pubmed ID: 23360025

Full thickness soft tissue defect over tibia is a big problem. Between December 2004 and July 2006, 20 patients of open Gustilo type IIIB tibial fractures were treated with fasciocutaneous flap after initial external fixation and control of infection done as evidenced by negative culture sensitivity test. The flap was chosen from the area between superior flexion crease of the calf at the popliteal fossa to the junction of the middle and inferior thirds of the posterior calf. The delay in flap surgery was mostly due to associated infection. Good results with satisfactory union were achieved in 85% cases. Infection occurred in 2 cases (10%). Marginal and full thickness necroses in this series were seen with sural flap; 2 cases (10%) developed partial necrosis of flap which was managed by skin graft and 1 (5%) developed full thickness necrosis. Fasciocutaneous flap helps in fracture union, control of infection and improves the functional outcome.

A Patient with Recurrent Attacks of Drowsiness and Lethargy--a Diagnosis Not to Be Missed

Journal of the Indian Medical Association. May, 2012  |  Pubmed ID: 23360028

Polyglandular auto-immune syndromes are uncommon constellation of organ specific auto-immune diseases, characterised by the existence of two or more endocrinopathies. Polyglandular autoimmune type II syndrome also known as Schmidt's syndrome is more common, comprising Addison's disease, auto-immune thyroid disease, type 1 diabetes mellitus and/or hypogonadism, pernicious anaemia, coeliac disease, vitiligo, hypophysitis, etc. Here a case of a 56-year-old man is reported with a prior history of hypothyroidism who presented with adrenal crisis. Further laboratory investigations revealed primary auto-immune hypothyroidism, primary adrenal insufficiency, hypogonadism and he was diagnosed as a case of polyglandular auto-immune type II syndrome or Schmidt's syndrome. Early recognition of the syndrome and replacement therapy can be life saving, particularly when there is adrenal or thyroid insufficiency.

Cell Block Cytology in Pleural Effusion

Journal of the Indian Medical Association. Jun, 2012  |  Pubmed ID: 23360042

Cell blocks prepared from residual tissue fluid can be used as adjuncts to smear for establishing a more definitive cytopathological diagnosis. It can be useful for categorisation also. Improved ethanol formalin fixative is used which offers excellent cytomorphologic features corresponding closely to cell in Papanicolaou stained smears. The technique is simple, safe, cost effective and reproducible even in resource limited rural areas. In this study among a total of 60 cases of suspected malignant pleural effusion, 56 were confirmed to be of malignant aetiology by all modalities. Only cell block preparation diagnosed 46 cases. Other modalities of diagnosis like bronchoscopy, broncho-alveolar lavage fluid study, fine needle aspiration cytology also have a great role in diagnosis. Twenty-two cases were diagnosed by Papanicolaou stain smear. So cell block preparation have more effective role in definitive diagnosis. It can be useful for better diagnosis in cases of poorly differentiated malignant neoplasms by immunocytochemistry.

Foreign Bodies in Bronchus--2 Years Experience at IPGME&R, Kolkata

Journal of the Indian Medical Association. Jun, 2012  |  Pubmed ID: 23360044

Foreign body in the bronchus is one of the life saving emergency in the ENT department. Most patients of foreign body bronchus are kids. Common presentation is respiratory distress or noisy respiration of sudden onset. Proper clinical examination and suspicion needed for proper diagnosis. In this report, 52 cases of foreign body bronchus were included. All patients underwent straight x-ray chest after taking proper history and while aroused suspicion. All of them received antibiotic and steroid. Foreign body was removed by rigid bronchoscope, flexible bronchoscope and by rigid telescope along with rigid bronchoscope. Most foreign bodies lodged in the left bronchus. Only one patient had died in the process for anaesthetic hazards.

Optical, Spectroscopic, and Doppler Evaluation of "normal" and "abnormal" Reflexology Areas in Lumbar Vertebral Pathology: a Case Study

Case Reports in Medicine. 2012  |  Pubmed ID: 23365581

Scientific validation of reflexology requires an in-depth and noninvasive evaluation of "reflexology/reflex areas" in health and disease. The present paper reports the differential properties of "normal" and "abnormal" reflexology areas related to the lumbar vertebrae in a subject suffering from low back pain. The pathology is supported by radiological evidence. The reflexology target regions were clinically assessed with respect to colour and tenderness in response to finger pressure. Grey scale luminosity and pain intensity, as assessed by visual analogue scale scores, differentiated "normal" from "abnormal" skin. Skin swept source-optical coherence tomography recorded their structural differences. Infrared thermography revealed temperature variations. A laser Doppler study using a combined microcirculation and transcutaneous oxygen monitoring system indicated alterations in blood flow and oxygen perfusion. Raman spectroscopy showed differences in chemical signatures between these areas. The present findings may indicate a potential correlation between the reflexology areas and subsurface pathological changes, showing an association with the healthy or unhealthy status of the lumbar vertebrae.

Detecting Parkinsons' Symptoms in Uncontrolled Home Environments: A Multiple Instance Learning Approach

Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference. Aug, 2012  |  Pubmed ID: 23366728

In this paper, we propose to use a weakly supervised machine learning framework for automatic detection of Parkinson's Disease motor symptoms in daily living environments. Our primary goal is to develop a monitoring system capable of being used outside of controlled laboratory settings. Such a system would enable us to track medication cycles at home and provide valuable clinical feedback. Most of the relevant prior works involve supervised learning frameworks (e.g., Support Vector Machines). However, in-home monitoring provides only coarse ground truth information about symptom occurrences, making it very hard to adapt and train supervised learning classifiers for symptom detection. We address this challenge by formulating symptom detection under incomplete ground truth information as a multiple instance learning (MIL) problem. MIL is a weakly supervised learning framework that does not require exact instances of symptom occurrences for training; rather, it learns from approximate time intervals within which a symptom might or might not have occurred on a given day. Once trained, the MIL detector was able to spot symptom-prone time windows on other days and approximately localize the symptom instances. We monitored two Parkinson's disease (PD) patients, each for four days with a set of five triaxial accelerometers and utilized a MIL algorithm based on axis parallel rectangle (APR) fitting in the feature space. We were able to detect subject specific symptoms (e.g. dyskinesia) that conformed with a daily log maintained by the patients.

Aging and Crossovers in Phase-separating Fluid Mixtures

Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics. Dec, 2012  |  Pubmed ID: 23367915

We use state-of-the-art molecular dynamics simulations to study hydrodynamic effects on aging during kinetics of phase separation in a fluid mixture. The domain growth law shows a crossover from a diffusive regime to a viscous hydrodynamic regime. There is a corresponding crossover in the autocorrelation function from a power-law behavior to an exponential decay. While the former is consistent with theories for diffusive domain growth, the latter results as a consequence of faster advective transport in fluids for which an analytical justification has been provided.

Entropy Hysteresis and Nonequilibrium Thermodynamic Efficiency of Ion Conduction in a Voltage-gated Potassium Ion Channel

Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics. Dec, 2012  |  Pubmed ID: 23367983

Here we have studied the nonequilibrium thermodynamic response of a voltage-gated Shaker potassium ion channel using a stochastic master equation. For a constant external voltage, the system reaches equilibrium indicated by the vanishing total entropy production rate, whereas for oscillating voltage the current and entropy production rates show dynamic hysteretic behavior. Here we have shown quantitatively that although the hysteresis loop area vanishes in low and high frequency domains of the external voltage, they are thermodynamically distinguishable. In the very low frequency domain, the system remains close to equilibrium, whereas at high frequencies it goes to a nonequilibrium steady state (NESS) associated with a finite value of dissipation function. At NESS, the efficiency of the ion conduction can also be related with the nonlinear dependence of the dissipation function on the power of the external field. Another intriguing aspect is that, at the high frequency limit, the total entropy production rate oscillates at NESS with half of the time period of the external voltage.

Early Regimes of Capillary Filling

Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics. Dec, 2012  |  Pubmed ID: 23368085

In this paper we analyze the inviscid regime (for which viscosity is unimportant and the flow occurs due to the balance between the capillary and the inertial effects) that invariably precedes the classical century-old Washburn regime during capillary filling. We demonstrate that a new nondimensional number, namely, the product of the Ohnesorge number and the ratio between the filling length (â„“) and the radius of the capillary (R), dictates the occurrence of this regime and the other well-known regimes in a capillary filling problem. We also identify that this inviscid regime occurs for the time that is of the order of the capillary time scale and, as has been quantified before [Quere, Eur. Phys. Lett. 39, 533 (1997); Joly, J. Chem. Phys. 135, 214705 (2011)], is characterized by the filling length being linearly proportional to the filling time. We establish the universality of this regime by pinpointing the existence of this regime (showing appropriate dependencies of the capillary radii and density) from existing experimental and Molecular Dynamics Simulation results that signify disparate ranges of length and time scales.

Observation of Sequential Υ Suppression in PbPb Collisions

Physical Review Letters. Nov, 2012  |  Pubmed ID: 23368113

The suppression of the individual Υ(nS) states in PbPb collisions with respect to their yields in pp data has been measured. The PbPb and pp data sets used in the analysis correspond to integrated luminosities of 150  μb^{-1} and 230  nb^{-1}, respectively, collected in 2011 by the CMS experiment at the LHC, at a center-of-mass energy per nucleon pair of 2.76 TeV. The Υ(nS) yields are measured from the dimuon invariant mass spectra. The suppression of the Υ(nS) yields in PbPb relative to the yields in pp, scaled by the number of nucleon-nucleon collisions, R_{AA}, is measured as a function of the collision centrality. Integrated over centrality, the R_{AA} values are 0.56±0.08(stat)±0.07(syst), 0.12±0.04(stat)±0.02(syst), and lower than 0.10 (at 95% confidence level), for the Υ(1S), Υ(2S), and Υ(3S) states, respectively. The results demonstrate the sequential suppression of the Υ(nS) states in PbPb collisions at LHC energies.

Contact Angles on a Soft Solid: From Young's Law to Neumann's Law

Physical Review Letters. Dec, 2012  |  Pubmed ID: 23368226

The contact angle that a liquid drop makes on a soft substrate does not obey the classical Young's relation, since the solid is deformed elastically by the action of the capillary forces. The finite elasticity of the solid also renders the contact angles differently from those predicted by Neumann's law, which applies when the drop is floating on another liquid. Here, we derive an elastocapillary model for contact angles on a soft solid by coupling a mean-field model for the molecular interactions to elasticity. We demonstrate that the limit of a vanishing elastic modulus yields Neumann's law or a variation thereof, depending on the force transmission in the solid surface layer. The change in contact angle from the rigid limit to the soft limit appears when the length scale defined by the ratio of surface tension to elastic modulus γ/E reaches the range of molecular interactions.

Cold-Nuclear-Matter Effects on Heavy-Quark Production in D+Au Collisions at Sqrt[s_{NN}]=200  GeV

Physical Review Letters. Dec, 2012  |  Pubmed ID: 23368311

The PHENIX experiment has measured electrons and positrons at midrapidity from the decays of hadrons containing charm and bottom quarks produced in d+Au and p+p collisions at sqrt[s_{NN}]=200  GeV in the transverse-momentum range 0.85≤p_{T}^{e}≤8.5  GeV/c. In central d+Au collisions, the nuclear modification factor R_{dA} at 1.5

Interaction Induced Staggered Spin-orbit Order in Two-dimensional Electron Gas

Physical Review Letters. Dec, 2012  |  Pubmed ID: 23368354

We propose and formulate an interaction induced staggered spin-orbit order as a new emergent phase of two-dimensional Fermi gases. We show that when some form of inherent spin splitting via Rashba-type spin-orbit coupling renders two helical Fermi surfaces to become significantly "nested," a Fermi surface instability arises. To lift this degeneracy, a spontaneous symmetry-breaking spin-orbit density wave develops, causing a surprisingly large quasiparticle gapping with chiral electronic states. Since the staggered spin-orbit order is associated with a condensation energy, quantified by the gap value, destroying such spin-orbit interaction costs sufficiently large perturbation field or temperature or dephasing time. The BiAg_{2} surface state is shown to be a representative system for realizing such novel spin-orbit interaction with tunable and large strength, and the spin splitting is decoupled from charge excitations. These functional properties are relevant for spin electronics, spin caloritronics, and spin-Hall effect applications.

Study of the Dijet Mass Spectrum in Pp→W+jets Events at Sqrt[s]=7  TeV

Physical Review Letters. Dec, 2012  |  Pubmed ID: 23368450

We report an investigation of the invariant mass spectrum of the two jets with highest transverse momentum in pp→W+2-jet and W+3-jet events to look for resonant enhancement. The data sample corresponds to an integrated luminosity of 5.0  fb^{-1} collected with the CMS detector at sqrt[s]=7  TeV. We find no evidence for the anomalous structure reported by the CDF Collaboration, and establish an upper limit of 5.0 pb at 95% confidence level on the production cross section for a generic Gaussian signal with mass near 150 GeV. Additionally, we exclude two theoretical models that predict a CDF-like dijet resonance near 150 GeV.

Pion, Kaon, and Proton Production in Central Pb-Pb Collisions at Sqrt[s_{NN}]=2.76  TeV

Physical Review Letters. Dec, 2012  |  Pubmed ID: 23368453

In this Letter we report the first results on π^{±}, K^{±}, p, and p[over ¯] production at midrapidity (|y|<0.5) in central Pb-Pb collisions at sqrt[s_{NN}]=2.76  TeV, measured by the ALICE experiment at the LHC. The p_{T} distributions and yields are compared to previous results at sqrt[s_{NN}]=200  GeV and expectations from hydrodynamic and thermal models. The spectral shapes indicate a strong increase of the radial flow velocity with sqrt[s_{NN}], which in hydrodynamic models is expected as a consequence of the increasing particle density. While the K/π ratio is in line with predictions from the thermal model, the p/π ratio is found to be lower by a factor of about 1.5. This deviation from thermal model expectations is still to be understood.

Measurement of the Cross Section for Electromagnetic Dissociation with Neutron Emission in Pb-Pb Collisions at Sqrt[s_{NN}]=2.76  TeV

Physical Review Letters. Dec, 2012  |  Pubmed ID: 23368454

The first measurement of neutron emission in electromagnetic dissociation of ^{208}Pb nuclei at the LHC is presented. The measurement is performed using the neutron zero degree calorimeters of the ALICE experiment, which detect neutral particles close to beam rapidity. The measured cross sections of single and mutual electromagnetic dissociation of Pb nuclei at sqrt[s_{NN}]=2.76  TeV with neutron emission are σ_{singleEMD}=187.4±0.2(stat)_{-11.2}^{+13.2}(syst)  b and σ_{mutualEMD}=5.7±0.1(stat)±0.4(syst)  b, respectively. The experimental results are compared to the predictions from a relativistic electromagnetic dissociation model.

Search for Heavy Neutrinos and W_{R} Bosons with Right-Handed Couplings in a Left-Right Symmetric Model in Pp Collisions at Sqrt[s]=7  TeV

Physical Review Letters. Dec, 2012  |  Pubmed ID: 23368549

Results are presented from a search for heavy, right-handed muon neutrinos, N_{μ}, and right-handed W_{R} bosons, which arise in the left-right symmetric extensions of the standard model. The analysis is based on a 5.0  fb^{-1} sample of proton-proton collisions at a center-of-mass energy of 7 TeV, collected by the CMS detector at the Large Hadron Collider. No evidence is observed for an excess of events over the standard model expectation. For models with exact left-right symmetry, heavy right-handed neutrinos are excluded at 95% confidence level for a range of neutrino masses below the W_{R} mass, dependent on the value of M_{W_{R}}. The excluded region in the two-dimensional (M_{W_{R}}, M_{N_{μ}}) mass plane extends to M_{W_{R}}=2.5  TeV.

Coherence-enhanced Optical Determination of the ^{229}th Isomeric Transition

Physical Review Letters. Dec, 2012  |  Pubmed ID: 23368553

The impact of coherent light propagation on the excitation and fluorescence of thorium nuclei in a crystal lattice environment is investigated theoretically. We find that in the forward direction, the fluorescence signal exhibits characteristic intensity modulations dominated by a sped-up initial decay signal that is orders of magnitude faster. This feature can be exploited for the optical determination of the isomeric transition energy. In order to obtain a unmistakable signature of the isomeric nuclear fluorescence, we put forward a novel scheme for the direct measurement of the transition energy via electromagnetically modified nuclear forward scattering involving two fields that couple to three nuclear states.

Assessment of Placental Oxidative Stress in Pre-eclampsia

Journal of Obstetrics and Gynaecology of India. Feb, 2012  |  Pubmed ID: 23372288

To study oxidative stress in placental tissue as well as in serum in pre-eclamptic women.

A Process-based Review of Mouse Models of Pulmonary Hypertension

Pulmonary Circulation. Oct, 2012  |  Pubmed ID: 23372926

Genetically modified mouse models have unparalleled power to determine the mechanisms behind different processes involved in the molecular and physiologic etiology of various classes of human pulmonary hypertension (PH). Processes known to be involved in PH for which there are extensive mouse models available include the following: (1) Regulation of vascular tone through secreted vasoactive factors; (2) regulation of vascular tone through potassium and calcium channels; (3) regulation of vascular remodeling through alteration in metabolic processes, either through alteration in substrate usage or through circulating factors; (4) spontaneous vascular remodeling either before or after development of elevated pulmonary pressures; and (5) models in which changes in tone and remodeling are primarily driven by inflammation. PH development in mice is of necessity faster and with different physiologic ramifications than found in human disease, and so mice make poor models of natural history of PH. However, transgenic mouse models are a perfect tool for studying the processes involved in pulmonary vascular function and disease, and can effectively be used to test interventions designed against particular molecular pathways and processes involved in disease.

Analysis of Factors Governing Dynamic Stiffness Index of Medical Compression Bandages

Biorheology. Jan, 2012  |  Pubmed ID: 23380903

Objective: To identify and analyze the important factors which could influence the Dynamic Stiffness Index (DSI) of compression bandages.Methods: Using three commercially available bandages with different stiffnesses, their DSI was obtained using a prototype based on an artificial leg-segment model consisting of a wooden mannequin having a variable circumference. The effect on DSI of three major factors, bandage extensibility (ε), resting pressure (RP) and limb circumference (C) was studied. An N-way ANOVA for a fixed model was carried out to test the significance of the above major factors and their interaction effects on bandage DSI.Results: There were significant differences (p<0.05) between the mean DSI observed at different values of ε, RP and C. It was also found that some of the factors, ε and RP, and C and RP, interfere with each other and that their interaction effects also significantly affected the DSI (p<0.05).Conclusion: The above major factors have a deciding influence on the DSI of the compression bandages. Understanding the influence of these factors and the effect of their interactions on the DSI could help in pre-evaluating and comparing dynamic behaviors of different compression bandages during compression management.

Effect of Garlic (Allium Sativum) on Hematology and Erythrocyte Antioxidant Defense System of Albino Rats Exposed to Heavy Metals (nickel II & Chromium VI)

Indian Journal of Physiology and Pharmacology. Apr-Jun, 2012  |  Pubmed ID: 23387242

Heavy metals are stable environmental contaminants, causing various alterations in target tissues. Garlic has some beneficial effect in preventing heavy metal induced various alteration. The objective was to investigate the possible protective role of fresh aqueous homogenate of garlic on hematology, erythrocyte antioxidant defense system in male albino rats treated with NiSO4 and K2Cr2O7. Rats were divided into six groups. Group I was untreated control. Group II was given aqueous homogenate of garlic (orally). Group III was administered with nickel sulfate (i.p). Group IV was given NiSO4 and garlic simultaneously. Group V was administered with K2Cr2O7 (i.p). Group VI were treated simultaneously with K2Cr2O7 and garlic. RBC, WBC, platelet count, PCV%, hemoglobin concentration decreased significantly and clotting time increased significantly after nickel treatment. After chromium treatment all the values decreased except clotting time. Increased malondialdehyde and glutathione level after nickel and chromium treatment was observed. Also erythrocyte superoxide dismutase, glutathione peroxidase and catalase activities significantly increased after nickel and chromium treatment. Simultaneous garlic supplementation exhibited protective role to combat nickel toxicity, whereas no such beneficial effects were observed for chromium (VI). Garlic may partially prevent nickel and chromium induced alteration but such ameliorated effects as an antioxidant is only restricted on nickel induced alteration.

Complicated Intra-abdominal Infections in a Worldwide Context: an Observational Prospective Study (CIAOW Study)

World Journal of Emergency Surgery : WJES. 2013  |  Pubmed ID: 23286785

ABSTRACT: Despite advances in diagnosis, surgery, and antimicrobial therapy, mortality rates associated with complicated intra-abdominal infections remain exceedingly high. The World Society of Emergency Surgery (WSES) has designed the CIAOW study in order to describe the clinical, microbiological, and management-related profiles of both community- and healthcare-acquired complicated intra-abdominal infections in a worldwide context. The CIAOW study (Complicated Intra-Abdominal infection Observational Worldwide Study) is a multicenter observational study currently underway in 57 medical institutions worldwide. The study includes patients undergoing surgery or interventional drainage to address complicated intra-abdominal infections. This preliminary report includes all data from almost the first two months of the six-month study period. Patients who met inclusion criteria with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study. 702 patients with a mean age of 49.2 years (range 18-98) were enrolled in the study. 272 patients (38.7%) were women and 430 (62.3%) were men. Among these patients, 615 (87.6%) were affected by community-acquired IAIs while the remaining 87 (12.4%) suffered from healthcare-associated infections. Generalized peritonitis was observed in 304 patients (43.3%), whereas localized peritonitis or abscesses was registered in 398 (57.7%) patients.The overall mortality rate was 10.1% (71/702). The final results of the CIAOW Study will be published following the conclusion of the study period in March 2013.

Sunset Yellow FCF, a Permitted Food Dye, Alters Functional Responses of Splenocytes at Non-cytotoxic Dose

Toxicology Letters. Jan, 2013  |  Pubmed ID: 23287708

Sunset yellow FCF (SY), a permitted food color, is extensively used in various food preparations and quite often exceeds the permissible levels (100-200mg/kg). Several toxicity studies on SY are reported, however immunomodulatory properties have not been explored yet. To investigate the immunotoxic properties of SY, splenocytes were isolated, cultured and subjected to mitogen stimulated proliferation assay (lipopolysaccharide, LPS or concanavalin A, Con A), mixed lymphocyte reaction (MLR) assay, immunophenotypic analysis of cell surface receptor expression and assay for cytokines release in the culture supernatants were performed in the presence of SY. Since SY did not exhibit any cytotoxicity up to 250μg/ml, this dose was used for further studies. It was observed that SY (250μg/ml) significantly (p<0.05) suppressed the mitogen induced proliferation of splenocytes and MLR response. Further, immunophenotypic analysis revealed that SY alters the relative expression of CD3e/CD4/CD8 in T cells and CD19 in B-cells. Consistent with the suppression of T-cell and B-cell responses and altered surface receptor expression, SY also lowered the expression of IL2, IL4, IL6, IL-17, IFN-γ and TNF-α cytokines. These results suggest that non-cytotoxic dose of SY may have immunomodulatory effects.

Novel Antineoplastics Targeting Genetic Changes in Colorectal Cancer

Advances in Experimental Medicine and Biology. 2013  |  Pubmed ID: 23288633

Cytotoxic chemotherapy remains the mainstay of the medical -management of colorectal cancer (CRC). Research over the last two decades has led to a molecular understanding of the oncogenic mechanisms involved in CRC and has contributed to the rational development of antineoplastics that target these mechanisms. During carcinogenesis, genetic changes often occur in molecules that play key functional roles in cancer such as cell proliferation, angiogenesis, apoptosis, cell death and immune-mediated destruction of cancer cells. Here, we review novel antineoplastics that are approved or in development for CRC that target molecules associated with genetic aberrations in CRC. Some of these targeted antineoplastics have proven effective against other solid tumors and hold promise in treating CRC whereas others are now routinely used in combination with cytotoxic agents. This article reviews antineoplastics that target genetic changes in CRC, their antitumor mechanisms, and their stage of development.

A Second Generation 2-Methoxyestradiol Prodrug is Effective Against Barrett's Adenocarcinoma in a Mouse Xenograft Model

Molecular Cancer Therapeutics. Jan, 2013  |  Pubmed ID: 23288782

2-Methoxyestradiol (2-ME2) is an endogenous metabolite of estradiol. Previous studies demonstrated that 2-ME2 is a potent antiproliferative, pro-apoptotic, antiangiogenic drug and exogenous 2-ME2 is effective against different types of tumors. Unfortunately, only low systemic concentrations of 2-ME2 can be achieved following oral administration, even after very high doses are administered to patients. The major barriers to high systemic levels of 2-ME2 include, but are not limited to, formulation, solubility, permeability, transporter effects, and first-pass metabolism. In an effort to solve this problem we have now synthesized and tested a new prodrug of 2-ME2 that is water soluble due to a bio-reversible hydrophilic group added at the 3-position and more effectively resists metabolic inactivation due to an ester moiety added to mask the 17-position alcohol. The 3-position modification is designed to be cleave by phosphatases at the brush-border of the intestinal epithelium to generate high local concentrations of the prodrug intermediate for intestinal absorption, and on the first-pass through the intestinal epithelium and liver, the masked 17-position will be de-esterified to produce active drug. We are reporting here for the first time that this double prodrug of 2-ME2 is effective as an antiproliferative and anti-cancer agent for both in vitro and in vivo studies against Barrett's esophageal adenocarcinoma (BEAC), and provided greater potency than 2-ME2 in inhibiting the growth of BEAC xenografts. Finally, studies indicate that, like 2-ME2, the 2-ME2-PD1 exhibits anticancer effect through disruption of microtubule-network.

Identification of the Activator Binding Residues in the Second Cysteine-Rich Regulatory Domain of Protein Kinase C Theta

The Biochemical Journal. Jan, 2013  |  Pubmed ID: 23289588

PKCθ is predominantly expressed in T-cells and critically involved in immunity. Design of PKCθ selective molecules to manage autoimmune disorders by targeting its activator binding C1 domain requires the knowledge of its structure and the activator binding residues. The C1 domain consists of twin C1 domains, C1A and C1B, of which C1B plays the critical role in the membrane translocation and activation of PKCq. Here, we determined the crystal structure of the PKCθC1B to 1.63Å resolution, which showed that the Trp-253 at the rim of the activator binding pocket was oriented towards the membrane whereas in PKCdC1B, the homologous tryptophan was oriented away from the membrane. This particular orientation of Trp-253 abolishes the possible p-stacking interactions between Trp-253 and His-270 and the cation-p interactions between Trp-253 and Arg-272, which are present between the homologous residues in PKCdC1B. To further probe the structural constraints on activator binding, five residues lining the activator binding site were mutated (Y239A, T243A, W253G, L255G and Q258G) and the binding affinities of the PKCθC1B mutants were measured. These mutants showed reduced binding affinities for phorbol ester (PDBu) and diacylglycerol (DOG). All the five full length PKCθ mutants exhibited reduced phorbol ester-induced membrane translocation compared to the wild type. These results provide insights into the PKCq activator binding domain, which will aid in future design of PKCθ selective molecules.

Gastrointestinal Mucormycosis: A Success Story and Appraisal of Concepts

Journal of Infection and Public Health. Feb, 2013  |  Pubmed ID: 23290094

Mucormycosis is an opportunistic, life-threatening fungal infection caused by fungi of the class Zygomycetes. The disease has traditionally been reported in immunocompromised patients, premature infants, diabetics, transplant recipients, prolonged use of corticosteroids or in condition associated with increased availability of serum iron such as acidosis or deferoxamine administration. The infection is progressive and associated with a high mortality unless treatment is initiated promptly. The number of cases of gastrointestinal mucormycosis indexed on PubMed over the past 2 decades has shown an alarming rise. Moreover, the infection is being increasingly reported in patients without the traditional risk factors. We report successful management of an immunocompetent child with gastrointestinal mucormycosis who responded to aggressive treatment with surgical debridement and antifungal agents. The fungicidal activity of colistin (polymyxin E) has also been highlighted.

Catechins and Osteoporosis

Nutrition (Burbank, Los Angeles County, Calif.). Jan, 2013  |  Pubmed ID: 23290097

A Cyclic Peptide Mimic of an RNA Recognition Motif of Human La Protein is a Potent Inhibitor of Hepatitis C Virus

Antiviral Research. Jan, 2013  |  Pubmed ID: 23291201

Due to limited available therapeutic options, developing new lead compounds against hepatitis C virus is an urgent need. Human La protein stimulates hepatitis C virus translation through interaction with the hepatitis C viral RNA. A cyclic peptide mimicking the β-turn of the human La protein that interacts with the viral RNA was synthesized. It inhibits hepatitis C viral RNA translation significantly better than the corresponding linear peptide at longer post-treatment times. The cyclic peptide also inhibited replication as measured by replicon RNA levels using real time RT-PCR. The cyclic peptide emerges as a promising lead compound against hepatitis C.

Mechanical Probes of SOD1 Predict Systematic Trends in Metal and Dimer Affinity of ALS-Associated Mutants

Journal of Molecular Biology. Jan, 2013  |  Pubmed ID: 23291526

Mutations and oxidative modification in the protein Cu,Zn superoxide dismutase (SOD1) have been implicated in the death of motor neurons in amyotrophic lateral sclerosis (ALS), a presently incurable, invariably fatal neurodegenerative disease. Here we employ steered, all-atom molecular dynamics simulations in implicit solvent to investigate the significance of either mutations or post-translational modifications (PTMs) to SOD1 on metal affinity, dimer stability, and mechanical malleability. The work required to induce moderate structural deformations as a function of sequence index constitutes a "mechanical fingerprint" measuring structural rigidity in the native basin, from which we are able to unambiguously distinguish wild-type SOD1 from PTM variants and measure the severity of a given PTM on structural integrity. The cumulative distribution of work values provided a way to cleanly discriminate between SOD1 variants. Disulfide reduction destabilizes dimer stability more than the removal of either metal, but not moreso than the removal of both metals. Intriguingly, we found that disulfide reduction mechanically stabilizes apo-SOD1 monomer, underscoring the differences between native basin mechanical properties and equilibrium thermodynamic stabilities and elucidating the presence of internal stress in the apo state. All PTMs and ALS-associated mutants studied showed an increased tendency to lose either Cu or Zn and to monomerize-processes known to be critical in the progression of ALS. The valence of Cu strongly modulates its binding free energy. As well, several mutants were more susceptible to loss of metals and monomerization than the disulfide-reduced or apo forms of SOD1. Distance constraints are required to calculate free energies for metal binding and dimer separation, which are validated using thermodynamic cycles. When distance constraints are removed, the results agree with those obtained from direct application of the Jarzynski equality.

Beneficial Effects of Grape Resveratrol on Serum Adiponectin and Inflammation: Clinical Trial in Patients with Stable Coronary Artery Disease : Editorial To: "Grape Resveratrol Increases Serum Adiponectin and Downregulates Inflammatory Genes in Peripheral Blood Mononuclear Cells: A Triple-Blind, Placebo-Controlled, One-Year Clinical Trial in Patients with Stable Coronary Artery Disease" by J. Tomé-Carneiro Et Al

Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. Feb, 2013  |  Pubmed ID: 23292168

DFT Studies on the Intrinsic Conformational Properties of Non-ionic Pyrrolysine in Gas Phase

Journal of Molecular Modeling. Jan, 2013  |  Pubmed ID: 23292322

B3LYP/6-31G(d,p) level of theory is used to carry out a detailed gas phase conformational analysis of non-ionized (neutral) pyrrolysine molecule about its nine internal back-bone torsional angles. A total of 13 minima are detected from potential energy surface exploration corresponding to the nine internal back-bone torsional angles. These minima are then subjected to full geometry optimization and vibrational frequency calculations at B3LYP/6-31++G(d,p) level. Characteristic intramolecular hydrogen bonds present in each conformer, their relative energies, theoretically predicted vibrational spectra, rotational constants and dipole moments are systematically reported. Single point calculations are carried out at B3LYP/6-311++G(d,p) and MP2/6-31++G(d,p) levels. Six types of intramolecular H-bonds, viz. O…H-O, N…H-O, O…H-N, N…H-N, O…H-C and N…H-C, are found to exist in the pyrrolysine conformers; all of which contribute to the stability of the conformers. The vibrational frequencies are found to shift invariably toward the lower side of frequency scale corresponding to the presence of intramolecular H-bond interactions in the conformers.

Discordance in Drug Resistance-associated Mutation Patterns in Marker Genes of Plasmodium Falciparum and Plasmodium Knowlesi During Coinfections

The Journal of Antimicrobial Chemotherapy. Jan, 2013  |  Pubmed ID: 23292346

OBJECTIVES: Human Plasmodium knowlesi infections have been reported from several South-East Asian countries, excluding India, but its drug susceptibility profile in mixed-infection cases remains unknown. METHODS: The chloroquine resistance transporter (CRT) and dihydrofolate reductase (DHFR) genes of P. knowlesi and other Plasmodium species were sequenced from clinical isolates obtained from malaria patients living in the Andaman and Nicobar Islands, India. The merozoite surface protein-1 and 18S rRNA genes of P. knowlesi were also sequenced from these isolates. RESULTS: Among 445 samples analysed, only 53 of them had P. knowlesi-specific gene sequences. While 3 of the 53 cases (5.66%) had P. knowlesi monoinfection, the rest were coinfected with Plasmodium falciparum (86.79%, n = 46) or Plasmodium vivax (7.55%, n = 4), but none with Plasmodium malariae or Plasmodium ovale. There was discordance in the drug resistance-associated mutations among the coinfecting Plasmodium species. This is because the P. knowlesi isolates contained wild-type sequences, while P. falciparum isolates had mutations in the CRT and DHFR marker genes associated with a higher level of chloroquine and antifolate drug resistance, respectively. The mutation pattern indicates that the same patient, having a mixed infection, may be harbouring the drug-susceptible P. knowlesi parasite and a highly drug-resistant P. falciparum parasite. CONCLUSIONS: A larger human population in South-East Asia may be at risk of P. knowlesi infection than reported so far. The different drug susceptibility genotypes of P. knowlesi from its coinfecting Plasmodium species in mixed infections adds a new dimension to the malaria control programme, requiring formulation of an appropriate drug policy.

Using Smooth Particle Hydrodynamics to Investigate Femoral Cortical Bone Remodelling at the Haversian Level

International Journal for Numerical Methods in Biomedical Engineering. Jan, 2013  |  Pubmed ID: 23293073

In the neck of the femur, about 70% of the strength is contributed by the cortical bone, which is the most highly stressed part of the structure and is the site where failure is almost certainly initiated. A better understanding of cortical bone remodelling mechanisms can help discern changes at this anatomical site, which are essential if an understanding of the mechanisms by which hips weaken and become vulnerable to fracture is to be gained. The aims of this study were to (i) examine a hypothesis that low strain fields arise because of subject-specific Haversian canal distributions causing bone resorption and reduced bone integrity and (ii) introduce the use of a meshless particle-based computational modelling approach SPH to capture bone remodelling features at the level of the Haversian canals. We show that bone remodelling initiated by strain at the Haversian level is highly influenced by the subject-specific pore distribution, bone density, loading and osteocyte density. SPH is shown to be effective at capturing the intricate bone pore shapes that evolved over time. Copyright © 2012 John Wiley & Sons, Ltd.

Hypothalamic Obesity: Prevalence, Associations and Longitudinal Trends in Weight in a Specialist Adult Neuroendocrine Clinic

European Journal of Endocrinology / European Federation of Endocrine Societies. Jan, 2013  |  Pubmed ID: 23293322

OBJECTIVE: Obesity is highly prevalent among adults with acquired, structural hypothalamic damage. We aimed to determine hormonal and neuroanatomical variables associated with weight gain and obesity in patients following hypothalamic damage, and to evaluate the impact of early instigation of weight loss measures to prevent or limit the severity of obesity in these patients. DESIGN: Retrospective study of 110 adults with hypothalamic tumours attending a specialist neuroendocrine clinic. Body mass index (BMI) was calculated at diagnosis and at last follow-up clinic visit. Endocrine data, procedures, treatments and weight loss measures were recorded and all available brain imaging reviewed. RESULTS: At last follow-up 82.7% of patients were overweight or heavier (BMI ≥ 25 kg/m2), 57.2% were obese (BMI ≥ 30 kg/m2), 14.5% were morbidly obese (BMI ≥ 40 kg/m2). Multivariate analysis revealed that use of desmopressin (odds ratio [OR] = 3.5; P = 0.026), growth hormone (OR = 2.7; P = 0.031) and thyroxine (OR = 3.0; P = 0.03) were associated with development of new or worsened obesity. Neuroimaging features were not associated with weight gain. Despite proactive treatments offered in clinic in recent years (counseling, dietetic and physical activity advice, anti-obesity medications), patients have continued to gain weight. CONCLUSIONS: Despite increased awareness hypothalamic obesity is difficult to prevent and to treat. Improved understanding of the underlying pathophysiologies and multicentre collaboration to examine efficacy of novel obesity interventions are warranted.

Interplay Between Drying and Stability of a TIM Barrel Protein: A Combined Simulation-Experimental Study

Journal of the American Chemical Society. Feb, 2013  |  Pubmed ID: 23293932

Recent molecular dynamics simulations have suggested important roles for nanoscale dewetting in the stability, function, and folding dynamics of proteins. Using a synergistic simulation-experimental approach on the αTS TIM barrel protein, we validated this hypothesis by revealing the occurrence of drying inside hydrophobic amino acid clusters and its manifestation in experimental measures of protein stability and structure. Cavities created within three clusters of branched aliphatic amino acids [isoleucine, leucine, and valine (ILV) clusters] were found to experience strong water density fluctuations or intermittent dewetting transitions in simulations. Individually substituting 10 residues in the large ILV cluster at the N-terminus with less hydrophobic alanines showed a weakening or diminishing effect on dewetting that depended on the site of the mutation. Our simulations also demonstrated that replacement of buried leucines with isosteric, polar asparagines enhanced the wetting of the N- and C-terminal clusters. The experimental results on the stability, secondary structure, and compactness of the native and intermediate states for the asparagine variants are consistent with the preferential drying of the large N-terminal cluster in the intermediate. By contrast, the region encompassing the small C-terminal cluster experiences only partial drying in the intermediate, and its structure and stability are unaffected by the asparagine substitution. Surprisingly, the structural distortions required to accommodate the replacement of leucine by asparagine in the N-terminal cluster revealed the existence of alternative stable folds in the native basin. This combined simulation-experimental study demonstrates the critical role of drying within hydrophobic ILV clusters in the folding and stability of the αTS TIM barrel.

Early Sepsis Does Not Increase the Risk of Late Sepsis in Very Low Birth Weight Neonates

The Journal of Pediatrics. Jan, 2013  |  Pubmed ID: 23295144

OBJECTIVE: To examine whether preterm very low birth weight (VLBW) infants have an increased risk of late-onset sepsis (LOS) following early-onset sepsis (EOS). STUDY DESIGN: Retrospective analysis of VLBW infants (401-1500 g) born September 1998 through December 2009 who survived >72 hours and were cared for within the National Institute of Child Health and Human Development Neonatal Research Network. Sepsis was defined by growth of bacteria or fungi in a blood culture obtained ≤72 hours of birth (EOS) or >72 hours (LOS) and antimicrobial therapy for ≥5 days or death <5 days while receiving therapy. Regression models were used to assess risk of death or LOS by 120 days and LOS by 120 days among survivors to discharge or 120 days, adjusting for gestational age and other covariates. RESULTS: Of 34 396 infants studied, 504 (1.5%) had EOS. After adjustment, risk of death or LOS by 120 days did not differ overall for infants with EOS compared with those without EOS [risk ratio (RR): 0.99 (0.89-1.09)] but was reduced in infants born at <25 weeks gestation [RR: 0.87 (0.76-0.99), P = .048]. Among survivors, no difference in LOS risk was found overall for infants with versus without EOS [RR: 0.88 (0.75-1.02)], but LOS risk was shorter in infants with birth weight 401-750 g who had EOS [RR: 0.80 (0.64-0.99), P = .047]. CONCLUSIONS: Risk of LOS after EOS was not increased in VLBW infants. Surprisingly, risk of LOS following EOS appeared to be reduced in the smallest, most premature infants, underscoring the need for age-specific analyses of immune function.

Arachidonic Acid and Lipoxin A(4) As Possible Endogenous Anti-diabetic Molecules

Prostaglandins, Leukotrienes, and Essential Fatty Acids. Jan, 2013  |  Pubmed ID: 23295193

In both type 1 and type 2 diabetes mellitus, increased production of pro-inflammatory cytokines and reactive oxygen species (ROS) occurs that induce apoptosis of β cells and cause peripheral insulin resistance respectively though the degree of their increased production is higher in type 1 and less in type 2 diabetes mellitus. Despite this, the exact mechanism(s) that lead to increased production of pro-inflammatory cytokines: interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and ROS is not known. Studies showed that plasma concentrations of arachidonic acid (AA) and lipoxin A(4) (LXA(4)) are low in alloxan-induced type 1 diabetes mellitus in experimental animals and patients with type 2 diabetes mellitus. Prior administration of AA, eicosapentaenoic and docosahexaenoic acids (EPA and DHA, respectively) and transgenic animals that produce increased amounts of EPA and DHA acids were protected from chemical-induced diabetes mellitus that was associated with enhanced formation of LXA(4) and resolvins, while protectin D(1) ameliorated peripheral insulin resistance. AA, LXA(4), resolvins and protectins inhibit IL-6 and TNF-α production and suppress ROS generation. Thus, AA and lipoxins, resolvins and protectins may function as endogenous anti-diabetic molecules implying that their administration could be useful in the prevention and management of both types of diabetes mellitus.

Corrected Profile Likelihood Confidence Interval for Binomial Paired Incomplete Data

Pharmaceutical Statistics. Jan, 2013  |  Pubmed ID: 23296487

Clinical trials often use paired binomial data as their clinical endpoint. The confidence interval is frequently used to estimate the treatment performance. Tang et al. (2009) have proposed exact and approximate unconditional methods for constructing a confidence interval in the presence of incomplete paired binary data. The approach proposed by Tang et al. can be overly conservative with large expected confidence interval width (ECIW) in some situations. We propose a profile likelihood-based method with a Jeffreys' prior correction to construct the confidence interval. This approach generates confidence interval with a much better coverage probability and shorter ECIWs. The performances of the method along with the corrections are demonstrated through extensive simulation. Finally, three real world data sets are analyzed by all the methods. Statistical Analysis System (SAS) codes to execute the profile likelihood-based methods are also presented. Copyright © 2013 John Wiley & Sons, Ltd.

The Ubiquitin Hydrolase UCH-L1 Destabilizes MTOR Complex 1 by Antagonizing DDB1-CUL4 Mediated Ubiquitination of Raptor

Molecular and Cellular Biology. Jan, 2013  |  Pubmed ID: 23297343

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates processes including mRNA translation, proliferation, and survival. By assembling with different cofactors, mTOR forms two complexes with distinct biological functions. Raptor-bound mTOR (mTORC1) governs cap-dependent mRNA translation, whereas mTOR, rictor, and mSin1 (mTORC2) activate the survival and proliferative kinase Akt. How the balance between the competing need for mTORC1 and 2 is controlled in normal cells and deregulated in disease is poorly understood. Here we show that the ubiquitin hydrolase UCH-L1 regulates the balance of mTOR signaling by disrupting mTORC1. We find that UCH-L1 impairs mTORC1 activity towards S6 kinase and 4EBP1 while increasing mTORC2 activity towards Akt. These effects are directly attributable to a dramatic rearrangement in mTOR complex assembly. UCH-L1 disrupts a complex between the DDB1-Cul4 ubiquitin ligase complex and raptor, and counteracts DDB1-Cul4 mediated raptor ubiquitination. These events lead to mTORC1 dissolution and a secondary increase in mTORC2. Experiments in Uchl1 deficient and transgenic mice suggest that the balance between these pathways is important for preventing neurodegeneration and the development of malignancy. These data establish UCH-L1 as a key regulator of the dichotomy between mTORC1 and mTORC2 signaling.

A Bottom-Up Approach Toward Fabrication of Ultrathin PbS Sheets

Nano Letters. Jan, 2013  |  Pubmed ID: 23297701

Two-dimensional (2D) sheets are currently in the spotlight of nanotechnology owing to high-performance device fabrication possibilities. Building a free-standing quantum sheet with controlled morphology is challenging when large planar geometry and ultranarrow thickness are simultaneously concerned. Coalescence of nanowires into large single-crystalline sheet is a promising approach leading to large, molecularly thick 2D sheets with controlled planar morphology. Here we report on a bottom-up approach to fabricate high-quality ultrathin 2D single crystalline sheets with well-defined rectangular morphology via collective coalescence of PbS nanowires. The ultrathin sheets are strictly rectangular with 1.8 nm thickness, 200-250 nm width, and 3-20 μm length. The sheets show high electrical conductivity at room and cryogenic temperatures upon device fabrication. Density functional theory (DFT) calculations reveal that a single row of delocalized orbitals of a nanowire is gradually converted into several parallel conduction channels upon sheet formation, which enable superior in-plane carrier conduction.

Positive Feedback Produces Broad Distributions in Maximum Activation Attained Within a Narrow Time Window in Stochastic Biochemical Reactions

The Journal of Chemical Physics. Jan, 2013  |  Pubmed ID: 23298061

How do single cell fate decisions induced by activation of key signaling proteins above threshold concentrations within a time interval are affected by stochastic fluctuations in biochemical reactions? We address this question using minimal models of stochastic chemical reactions commonly found in cell signaling and gene regulatory systems. Employing exact solutions and semi-analytical methods we calculate distributions of the maximum value (N) of activated species concentrations (P(max)(N)) and the time (t) taken to reach the maximum value (P(max)(t)) within a time interval in the minimal models. We find, the presence of positive feedback interactions make P(max)(N) more spread out with a higher "peakedness" in P(max)(t). Thus positive feedback interactions may help single cells to respond sensitively to a stimulus when cell decision processes require upregulation of activated forms of key proteins to a threshold number within a time window.

Evaluation of Superficial Dosimetry Between Treatment Planning System and Measurement for Several Breast Cancer Treatment Techniques

Medical Physics. Jan, 2013  |  Pubmed ID: 23298084

Purpose: Dosimetric accuracy in radiation treatment of breast cancer is critical for the evaluation of cosmetic outcomes and survival. It is often considered that treatment planning systems (TPS) may not be able to provide accurate dosimetry in the buildup region. This was investigated in various treatment techniques such as tangential wedges, field-in-field (FF), electronic compensator (eComp), and intensity-modulated radiotherapy (IMRT).Methods: Under Institutional Review Board (IRB) exemption, radiotherapy treatment plans of 111 cases were retrospectively analyzed. The distance between skin surface and 95% isodose line was measured. For measurements, Gafchromic EBT2 films were used on a humanoid unsliced phantom. Multiple layers of variable thickness of superflab bolus were placed on the breast phantom and CT scanned for planning. Treatment plans were generated using four techniques with two different grid sizes (1 × 1 and 2.5 × 2.5 mm(2)) to provide optimum dose distribution. Films were placed at different depths and exposed with the selected techniques. A calibration curve for dose versus pixel values was also generated on the same day as the phantom measurement was conducted. The DICOM RT image, dose, and plan data were imported to the in-house software. On axial plane of CT slices, curves were drawn at the position where EBT2 films were placed, and the dose profiles on the lines were acquired. The calculated and measured dose profiles were separated by check points which were marked on the films before irradiation. The segments of calculated profiles were stretched to match their resolutions to that of film dosimetry.Results: On review of treatment plans, the distance between skin and 95% prescribed dose was up to 8 mm for plans of 27 patients. The film measurement revealed that the medial region of phantom surface received a mere 45%-50% of prescribed dose. For wedges, FF, and eComp techniques, region around the nipple received approximately 80% of prescribed dose, although only IMRT showed inhomogeneous dose profile. At deeper depths mainly (6-11 mm depths), film dosimetry showed good agreement with the TPS calculation. In contrast, the measured dose at a 3-mm depth was higher than TPS calculation by 15%-30% for all techniques. For the tangential and IMRT techniques, 1 × 1 mm(2) grid size showed a smaller difference than that with a 2.5 × 2.5 mm(2) grid size compared to the measurements.Conclusions: In general, TPS even with advanced algorithms do not provide accurate dosimetry in the buildup region, as verified by EBT2 film for all treatment techniques. For all cases, TPS and measured doses were in agreement from 6 mm in depth but differed at shallower depths. Grid size plays an important role in dose calculation. For accurate dosimetry small grid size should be used where differences are lower between TPS and measurements.

Plant-derived Human Collagen Scaffolds for Skin Tissue Engineering

Tissue Engineering. Part A. Jan, 2013  |  Pubmed ID: 23298216

Tissue engineering scaffolds are commonly formed using proteins extracted from animal tissues such as bovine hide. Risks associated with the use of these materials include hypersensitivity, and pathogenic contamination. Human-derived proteins lower the risk of hypersensitivity but possess the risk of disease transmission. Methods engineer recombinant human proteins using plant material provide an alternate source of these materials without the risk of disease transmission or concerns regarding variability. To investigate the utility of plant-derived human collagen (PDHC) in the development of engineered skin, PDHC and bovine hide collagen were formed into tissue engineering scaffolds using electrospinning or freeze-drying. Both raw materials were easily formed into two common scaffold types, electrospun nonwoven scaffolds and lyophilized sponges, with similar architectures. Processing time, however, was significantly lower with PDHC. PDHC scaffolds supported primary human cell attachment and proliferation at an equivalent or higher level than bovine material. IL-1 beta production was significantly lower when activated THP-1 macrophages where exposed to PDHC electrospun scaffolds compared to bovine collagen. Both materials promoted proper maturation and differentiation of engineered skin. These data suggest that PDHC may provide a novel source of raw material for tissue engineering with low risk of allergic response or disease transmission.

Antipyrine Based Arsenate Selective Fluorescent Probe for Living Cell Imaging

Analytical Chemistry. Feb, 2013  |  Pubmed ID: 23298301

Condensation of salicylaldehyde and 4-aminoantipyrine has yielded a new fluorescent probe (APSAL) capable of detecting intracellular arsenate at the micromolar level for the first time. The structure of the probe has been established by different spectroscopic techniques and confirmed from X-ray crystallography. Common anions, viz., F(-), Cl(-), Br(-), I(-), N(3)(-), NCO(-), NO(2)(-), NO(3)(-), SCN(-), CN(-), CH(3)COO(-), SO(4)(2-), ClO(4)(-), and HPO(4)(2-) do not interfere. The binding constant of APSAL for H(2)AsO(4)(-) has been determined using the Benesi-Hildebrand equation as 8.9 × 10(3) M(-1). Fluorescence quantum yield of APSAL (0.016) increases more than 12 times upon binding arsenate ion.

Subacute Oral Toxicity of Combinations of Selected Synthetic Pyrethroids, Piperonyl Butoxide, and Tetramethrin in Rats

Toxicology and Industrial Health. Jan, 2013  |  Pubmed ID: 23299193

In this study, 70 Wistar rats were randomly divided into seven equal groups (six experimental and one control), which consisted of animals belonging to both sexes. Different combinations of insecticides were administered daily to the experimental groups (group 1: cypermethrin + piperonyl butoxide (PBO); group 2: alphacypermethrin + PBO; group 3: deltamethrin + PBO; group 4: cypermethrin + PBO + tetramethrin; group 5: alphacypermethrin + PBO + tetramethrin; and group 6: deltamethrin + PBO + tetramethrin) for 28 days. During the study period, mortality and serious clinical findings were not observed in any animal. However, feed consumptions decreased in groups 1 and 3 (p < 0.05). Red blood cells, white blood cells, and hemoglobin levels, especially in cypermethrin and alphacypermethrin groups (groups 1, 2, and 4), were found to be higher than the control group (p < 0.05). Furthermore, biochemical changes related to liver, kidney functions, and protein metabolism occurred in males of almost all the groups. Relative liver and kidney weights of the male animals increased in the cypermethrin and alphacypermethrin groups (p < 0.05). The most common finding observed during the histopathological examination of all the experimental groups was centrilobular degeneration in the liver. It was concluded that although clinical symptoms were not observed, synthetic pyrethroid, synergist, and knockdown agent combinations might cause serious abnormalities when administered in certain doses in mammalians.

Some Case Studies on Application of "r(m) (2) " Metrics for Judging Quality of Quantitative Structure-activity Relationship Predictions: Emphasis on Scaling of Response Data

Journal of Computational Chemistry. Jan, 2013  |  Pubmed ID: 23299630

Quantitative structure-activity relationship (QSAR) techniques have found wide application in the fields of drug design, property modeling, and toxicity prediction of untested chemicals. A rigorous validation of the developed models plays the key role for their successful application in prediction for new compounds. The r(m) (2) metrics introduced by Roy et al. have been extensively used by different research groups for validation of regression-based QSAR models. This concept has been further advanced here with introduction of scaling of response data prior to computation of r(m) (2) . Further, a web application (accessible from and for calculation of the r(m) (2) metrics has been introduced here. The present study reports that the web application can be easily used for computation of r(m) (2) metrics provided observed and QSAR-predicted data for a set of compounds are available. Further, scaling of response data is recommended prior to r(m) (2) calculation. © 2013 Wiley Periodicals, Inc.

NIR- and FRET-Based Sensing of Cu(2+) and S(2-) in Physiological Conditions and in Live Cells

Inorganic Chemistry. Jan, 2013  |  Pubmed ID: 23302031

We have synthesized a new indole functionalized rhodamine derivative L(1) which specifically binds to Cu(2+) in the presence of large excess of other competing ions with visually observable changes in their electronic and fluorescence spectral behavior. These spectral changes are significant enough in the NIR and visible region of the spectrum and thus enable naked eye detection. The receptor, L(1), could be employed as a resonance energy transfer (RET) based sensor for detection of Cu(2+) based on the process involving the donor indole and the acceptor Cu(2+) bound xanthene fragment. Studies reveal that L(1)-Cu complex is selectively and fully reversible in presence of sulfide anions. Further, fluorescence microscopic studies confirmed that the reagent L(1) could also be used as an imaging probe for detection of uptake of these ions in HeLa cells.

Cardiomyocyte Proliferation Contributes to Heart Growth in Young Humans

Proceedings of the National Academy of Sciences of the United States of America. Jan, 2013  |  Pubmed ID: 23302686

The human heart is believed to grow by enlargement but not proliferation of cardiomyocytes (heart muscle cells) during postnatal development. However, recent studies have shown that cardiomyocyte proliferation is a mechanism of cardiac growth and regeneration in animals. Combined with evidence for cardiomyocyte turnover in adult humans, this suggests that cardiomyocyte proliferation may play an unrecognized role during the period of developmental heart growth between birth and adolescence. We tested this hypothesis by examining the cellular growth mechanisms of the left ventricle on a set of healthy hearts from humans aged 0-59 y (n = 36). The percentages of cardiomyocytes in mitosis and cytokinesis were highest in infants, decreasing to low levels by 20 y. Although cardiomyocyte mitosis was detectable throughout life, cardiomyocyte cytokinesis was not evident after 20 y. Between the first year and 20 y of life, the number of cardiomyocytes in the left ventricle increased 3.4-fold, which was consistent with our predictions based on measured cardiomyocyte cell cycle activity. Our findings show that cardiomyocyte proliferation contributes to developmental heart growth in young humans. This suggests that children and adolescents may be able to regenerate myocardium, that abnormal cardiomyocyte proliferation may be involved in myocardial diseases that affect this population, and that these diseases might be treatable through stimulation of cardiomyocyte proliferation.

Novel Lanthanide-labeled Metal Oxide Nanoparticles Improve the Measurement of in Vivo Clearance and Translocation

Particle and Fibre Toxicology. 2013  |  Pubmed ID: 23305071

ABSTRACT: The deposition, clearance and translocation of europium-doped gadolinium oxide nanoparticles in a mouse lung were investigated experimentally. Nanoparticles were synthesized by spray flame pyrolysis. The particle size, crystallinity and surface properties were characterized. Following instillation, the concentrations of particles in organs were determined with inductively coupled plasma mass spectrometry. The protein corona coating the nanoparticles was found to be similar to the coating on more environmentally relevant nanoparticles such as iron oxide. Measurements of the solubility of the nanoparticles in surrogates of biological fluids indicated very little propensity for dissolution, and the elemental ratio of particle constituents did not change, adding further support to the contention that intact nanoparticles were measured. The particles were intratracheally instilled into the mouse lung. After 24 hours, the target organs were harvested, acid digested and the nanoparticle mass in each organ was measured by inductively coupled plasma mass spectrometry (ICP-MS). The nanoparticles were detected in all the studied organs at low ppb levels; 59% of the particles remained in the lung. A significant amount of particles was also detected in the feces, suggesting fast clearance mechanisms. The nanoparticle system used in this work is highly suitable for quantitatively determining deposition, transport and clearance of nanoparticles from the lung, providing a quantified measure of delivered dose.

Enhanced Redifferentiation of Chondrocytes on Microperiodic Silk/gelatin Scaffolds: Toward Tailor-made Tissue Engineering

Biomacromolecules. Feb, 2013  |  Pubmed ID: 23305127

Direct-write assembly allows rapid fabrication of complex three-dimensional (3D) architectures, such as scaffolds simulating anatomical shapes, avoiding the need for expensive lithographic masks. However, proper selection of polymeric ink composition and tailor-made viscoelastic properties are critically important for smooth deposition of ink and shape retention. Deposition of only silk solution leads to frequent clogging due to shear-induced β-sheet crystallization, whereas optimized viscoelastic property of silk-gelatin blends facilitate the flow of these blends through microcapillary nozzles of varying diameter. This study demonstrates that induction of controlled changes in scaffold surface chemistry, by optimizing silk-gelatin ratio, can govern cell proliferation and maintenance of chondrocyte morphology. Microperiodic silk-gelatin scaffolds can influence postexpansion redifferentiation of goat chondrocytes by enhancing Sox-9 gene expression, aggregation, and driving cartilage matrix production, as evidenced by upregulation of collagen type II and aggrecan expression. The strategy for optimizing redifferentiation of chondrocytes can offer valuable consideration in scaffold-based cartilage repair strategies.

The Kinase Domain of Drosophila Tribbles is Required for Turnover of Fly C/EBP During Cell Migration

Developmental Biology. Jan, 2013  |  Pubmed ID: 23305818

Drosophila Tribbles (Trbl) encodes the founding member of the Trib family of kinase-like proteins that regulate cell migration, proliferation, growth and homeostasis. Trbl was identified in a misexpression screen in the ovary as an antagonist of border cell migration and acts in part by directing turnover of the C/EBP protein encoded by the gene slow border cells (slbo). The ability of mammalian Trib isoforms to promote C/EBP turnover during tissue differentiation indicates that this function is highly conserved. To better understand the role of Trbl in cell migration, we tested specific Trbl antisera, a trbl null allele and Trbl transgenes bearing site-directed mutations. Trbl is expressed at high levels in the nuclei of follicle cell epithelia and is downregulated in delaminating epithelia as expression of Slbo (C/EBP) is upregulated. This complementary pattern of expression during subsequent cell migration is achieved by negative feedback whereby slbo represses Trbl expression and trbl is necessary and sufficient to promote Slbo protein turnover. A series of point mutations that scan the conserved kinase domain of Trbl reveal that the conserved DLK catalytic loop is required for Trbl-Slbo binding and turnover, as well as for interactions between Trbl subunits, suggesting a mechanism of Trbl function.

Mitochondrial Dysfunction Contributes to the Cytotoxicity of Some 3,5-bis(benzylidene)-4-piperidone Derivatives in Colon HCT-116 Cells

Bioorganic & Medicinal Chemistry Letters. Feb, 2013  |  Pubmed ID: 23305919

The objectives of this study are to investigate the possible ways by which the curcumin analogs 2a and 2b exert their antiproliferative properties. The analogs 2a and 2b have submicromolar IC(50) values towards human HCT-116 colon cancer cells but are far less toxic to human non-malignant CRL-1790 colon cells. Both compounds affected a number of mitochondrial functions in HCT-116 cells namely increasing the intracellular concentrations of reactive oxygen species, inhibiting oxygen consumption and decreasing the mitochondrial membrane potential. These molecules also produced swelling of isolated rat liver mitochondria, supporting a mitochondrial mechanism of cytotoxicity. Both compounds reacted with glutathione in the presence of glutathione S-transferase π and hence they may be classified as thiol alkylators.

Cannabidiol Enhances Consolidation of Explicit Fear Extinction in Humans

Psychopharmacology. Jan, 2013  |  Pubmed ID: 23307069

RATIONALE: Whilst Cannabidiol (CBD), a non-psychotomimetic cannabinoid, has been shown to enhance extinction learning in rats, its effects on fear memory in humans have not previously been studied. OBJECTIVES: We employed a Pavlovian fear-conditioning paradigm in order to assess the effects of CBD on extinction and consolidation. METHOD: Forty-eight participants were conditioned to a coloured box (CS) with electric shocks (UCS) in one context and were extinguished in a second context. Participants received 32 mg of CBD either following before or after extinction in a double-blind, placebo-controlled design. At recall, 48 h later, participants were exposed to CSs and conditioning contexts before (recall) and after (reinstatement) exposure to the UCS. Skin conductance and shock expectancy measures of conditioned responding were recorded throughout. RESULTS: Successful conditioning, extinction and recall were found in all three treatment groups. CBD given post-extinction enhanced consolidation of extinction learning as assessed by shock expectancy. CBD administered at either time produced trend level reduction in reinstatement of autonomic contextual responding. No acute effects of CBD were found on extinction. CONCLUSIONS: These findings provide the first evidence that CBD can enhance consolidation of extinction learning in humans and suggest that CBD may have potential as an adjunct to extinction-based therapies for anxiety disorders.

Intra-arterial Allogeneic Mesenchymal Stem Cells for Critical Limb Ischemia Are Safe and Efficacious: Report of a Phase I Study

World Journal of Surgery. Jan, 2013  |  Pubmed ID: 23307180

BACKGROUND: Critical limb ischemia (CLI) caused by peripheral arterial disease is associated with significant morbidity and mortality. This condition is associated with a 30 % amputation rate as well as mortality levels which might be as high as 25 %. There is no pharmacological therapy available, but several reports have suggested that mesenchymal stem cells (MSCs) may be a useful therapeutic option. METHODS: This study, done at a university hospital, evaluated 13 patients for a phase I trial to investigate the safety and efficacy of intra-arterial MSCs in CLI patients. Eight patients with ten affected limbs were recruited for the study. As two patients (three limbs) died of ischemic cardiac events during the 6-month follow-up period, seven limbs were finally evaluated for the study. RESULTS: There was significant pain relief. Visual analog scale (VAS) scores decreased from 2.29 ± 0.29 to 0.5 ± 0.34 (p < 0.05), ankle brachial pressure index (ABPI) increased significantly from 0.56 ± 0.02 to 0.67 ± 0.021 (p < 0.01), and transcutaneous oxygen pressure (TcPO(2)) also increased significantly in the foot from 13.57 ± 3.63 to 38 ± 3.47. Similar improvement was seen in the leg as well as the thigh. There was 86 % limb salvage and six of seven ulcers showed complete or partial healing. CONCLUSION: It was concluded that intra-arterial MSCs could be safely administered to patients with CLI and was associated with significant therapeutic benefits.

Prediction of Zn Concentration in Human Seminal Plasma of Normospermia Samples by Artificial Neural Networks (ANN)

Journal of Assisted Reproduction and Genetics. Jan, 2013  |  Pubmed ID: 23307446

PURPOSE: There has been an increasing interest in the evaluation of metal ion concentration, present in different body fluids. It is known that metal ions, especially zinc play vital role in the fertility of human semen. OBJECTIVE: The main objective of the study is to evaluate the Zn concentration in Normospermia samples by Atomic absorption spectroscopy (AAS) and to predict the same by artificial neural network (ANN). MATERIALS AND METHODS: Normospermia semen samples were collected from the patients who came to attend semen analysis at Bangalore assisted conception centre, Bangalore, India. Semen analysis was done according to World Health Organization (WHO) guidance. Atomic absorption spectroscopy was used to estimate the total Zn in these samples, while the Back propagation neural network algorithm (BPNN) was used to predict the Zn levels in these samples. RESULTS: Zinc concentration obtained by AAS and BPNN indicated that there was a good correlation between the estimated and predicted values and was also found to be statistically significant. CONCLUSION: The BPNN algorithm developed in this study could be used for the prediction of Zn concentration in human Normospermia samples. FUTURE PERSPECTIVE: The algorithm could be further developed to predict the concentration of all the trace elements present in human seminal plasma of different infertile categories.

Charged-based Forces at the Nafion-water Interface

Langmuir : the ACS Journal of Surfaces and Colloids. Jan, 2013  |  Pubmed ID: 23311934

Interfacial water lying next to hydrophilic surfaces has been shown to be spectroscopically, mechanically, and electrically distinct from bulk water. Interfacial water has also been shown to exclude negatively- and positively-charged microspheres, and has thus become known as the "exclusion zone". Measurements have demonstrated that exclusion zones exhibit a negative electrical potential on the order of -100 mV relative to bulk water, with a corresponding distribution of positive protons in the bulk water region beyond the exclusion zone. This separation of charge is hypothesized to create an electrostatic force between the exclusion zone and the proton-enriched zone beyond. To test this hypothesis, a hydrophilic Nafion ring was attached to the tip of a deflectable ribbon-like force sensor. The sensor was designed to obstruct the flow of protons from one side of the lever to the other, so that any proton-based force would remain unilateral. pH-sensitive dye measurements confirmed that the protons were largely confined to one side. When the lever assembly was exposed to water, the sensor deflected toward the protons. Over a period of 20 min, deflection amounted to approximately 20 μm, corresponding to a force of approximately 22 μN. Hence, electrostatic forces are confirmed. If exclusion zones exist ubiquitously at hydrophilic surfaces, including biological surfaces, then the resulting electrostatic forces may play significant roles in many biological phenomena including adhesion and protein folding.

Analysis of Single Nucleotide Polymorphisms and Radiation Sensitivity of the Lung Assessed With an Objective Radiologic Endpoint

Clinical Lung Cancer. Jan, 2013  |  Pubmed ID: 23313170

BACKGROUND: The primary objective of this study was to evaluate the association between radiation sensitivity of the lungs and candidate single nucleotide polymorphisms (SNP) in genes implicated in radiation-induced toxicity. METHODS: Patients with lung cancer who received radiation therapy (RT) had pre-RT and serial post-RT single photon emission computed tomography (SPECT) lung perfusion scans. RT-induced changes in regional perfusion were related to regional dose, which generated patient-specific dose-response curves (DRC). The slope of the DRC is independent of total dose and the irradiated volume, and is taken as a reflection of the patient's inherent sensitivity to RT. DNA was extracted from blood samples obtained at baseline. SNPs were determined by using a combination of high-resolution melting, TaqMan assays, and direct sequencing. Genotypes from 33 SNPs in 22 genes were compared against the slope of the DRC by using the Kruskal-Wallis test for ordered alternatives. RESULTS: Thirty-nine self-reported Caucasian patients with pre-RT and ≥6 month post-RT SPECTs, and blood samples were identified. An association between genotype and increasing slope of the DRC was noted in G(1301) A in XRCC1 (rs25487) (P = .01) and G(3748) A in BRCA1 (rs16942) (P = .03). CONCLUSIONS: By using an objective radiologic assessment, polymorphisms within genes involved in repair of DNA damage (XRCC1 and BRCA1) were associated with radiation sensitivity of the lungs.

Copper Induced Immunotoxicity Promote Differential Apoptotic Pathways in Spleen and Thymus

Toxicology. Jan, 2013  |  Pubmed ID: 23313662

Inorganic copper, such as that in drinking water and copper supplements, largely bypasses the liver and enters the free copper pool of the blood directly and that promote immunosuppression. Nevertheless, the signaling pathways underlying copper-induced immune cell death remains largely unclear. According to our previous in vivo report, to evaluate the further details of the apoptotic mechanism, we have investigated how copper regulates apoptotic pathways in spleen and thymus. We have analyzed different protein expression by western blotting and immunohistochemistry and mRNA expression by RT-PCR and gel electrophoresis. We also have measured mitochondrial trans-membrane potential, ROS and CD4(+) and CD8(+) population by flow cytometry. Sub lethal doses of copper in spleen and thymus of in vivo Swiss albino mice promote different apoptotic pathways. In case of spleen, ROS generation and mitochondrial trans-membrane potential changes promotes intrinsic pathway of apoptosis that was p53 independent, ultimately leads to decrease in CD4(+) T cell population and increase in CD8(+) T cell population. However in case of thymus, ROS generation and mitochondrial trans-membrane potential changes lead to death receptor that regulate extrinsic and intrinsic pathways of apoptosis and the apoptotic mechanism which was p53 dependent. Due to copper treatment, thymic CD4(+) T cell population decreased and CD8(+) T cell population was increased or proliferated. Apart from the role of inflammation, our findings also have identified the role of other partially responsible apoptotic molecules like p27, p73, p62, poly (ADP-ribose) polymerase (PARP) that differentially changed due to copper treatment in spleen and thymus of Swiss albino mice. Present study firstly demonstrates how apoptotic pathways differentially regulate copper induced immunosuppression.

Cellular and Molecular Mechanisms of Accelerated Fracture Healing by COX2 Gene Therapy: Studies in a Mouse Model of Multiple Fractures

Bone. Jan, 2013  |  Pubmed ID: 23314071

This study sought to determine the cellular and molecular mechanisms of cyclooxygenase-2 (COX2) gene therapy to accelerate fracture repair in a mouse multiple tibial fractures model. The lenti-COX2 (or lenti-gfp control vector) was injected into fractures on day 1 post-fracture. At days 3-7, the COX2 treatment increased Sdf1-, Cxcr4-, Nes-, and Podxl-expressing mesenchymal stem cells (MSCs) within fracture calluses, suggesting an enhanced MSC recruitment or expansion. The COX2-treated mice formed smaller cartilaginous calluses that had less cartilage tissues than control mice. The expression of Sox9 mRNA was 7-fold less in COX2-treated than in control calluses at day 14, implying that COX2 reduces chondrocytic differentiation of MSCs. The therapy also enhanced angiogenesis as reflected by increased immunostaining of CD31, vWF, and α-SMA over controls in the cartilaginous callus at day 14-21. At which time, the COX2 gene therapy promoted bony remodeling of the cartilaginous callus to bridge the fracture gap that was accompanied by 2-fold increase in osteoclasts along the surface of the woven bone and an onset of osteogenesis. Blocking angiogenesis with daily injection of endostatin from day 4 to day 10 into fracture sites blocked the COX2-mediated reduction of callus size that was associated with an increase in hypertrophic chondrocytes and concomitant reduction in osteoclasts. In conclusion, COX2 accelerates fracture healing in part through three biological actions: 1) increased recruitment/expansion of MSCs; 2) decreased cartilaginous callus formation; and 3) increased angiogenesis-dependent cartilage remodeling. These effects were associated with an earlier onset of bony bridging of the fracture gap.

Asystole and Facial Pain

Practical Neurology. Feb, 2013  |  Pubmed ID: 23315460

Characterization of an Acid-inducible Sulfatase in Salmonella Enterica Serovar Typhimurium

Applied and Environmental Microbiology. Jan, 2013  |  Pubmed ID: 23315743

Sulfatases of enteric bacteria can provide access to heavily sulfated mucosal glycans. In this study we show that aslA (STM0084) of S. Typhimurium LT2 encodes a sulfatase that requires mildly acidic pH for its expression and activity. AslA is not regulated by sulfur compounds or tyramine but requires EnvZ-OmpR as well as PhoPQ regulatory systems that play an important role in pathogenesis.

Genetic Study on Frontotemporal Lobar Degeneration in India

Parkinsonism & Related Disorders. Jan, 2013  |  Pubmed ID: 23317568

Cystic Schwannoma of the Pelvis

Annals of the Royal College of Surgeons of England. Jan, 2013  |  Pubmed ID: 23317707

Schwannomas are benign tumours that arise from the Schwann cells of nerve fibres. They commonly occur in the head and neck, mediastinum and extremities. They are extremely rare in the pelvis. These are usually slow-growing tumours and are often detected incidentally. Preoperative diagnosis is extremely difficult as there are no definitive signs on imaging. Aspiration biopsy is often inconclusive or misleading. Surgical excision is both diagnostic and therapeutic. As these tumours are often large in size, open excision is most commonly performed. We describe a case of a large, cystic schwannoma of the pelvis causing bladder outlet obstruction and bilateral hydroureteronephrosis. Complete surgical excision was performed laparoscopically.

Post Tsunami Psychological Impact Among Survivors in Aceh and West Sumatra, Indonesia

Comprehensive Psychiatry. Jan, 2013  |  Pubmed ID: 23318005

OBJECTIVE: In 2004, the province of Aceh, Indonesia was rocked by tsunami and in September 2009, West Sumatra, Indonesia was hit by an earthquake. The aim of this study was to determine the long-term psychological impact on the residents inhabiting these regions and to identify factors associated with it. METHODS: A cross-sectional study was conducted among the residents. The Depression, Anxiety and Stress Scale (DASS) was used to measure their psychological well-being. RESULTS: Out of 200 respondents, 1 in 5 (19%) was found to suffer from a high level of depression, 1 in 2 (51%) had anxiety and 1 in 5 (22%) experienced stress. Factors found to be significantly associated with depression, anxiety and stress were female, young age, unemployed, and single (p<0.05). CONCLUSION: The psychological impact following the tsunami persisted in the population after many years post-disaster. It is recommended that the psychological profile of the population be evaluated for the vulnerable group following any natural disaster.

Impact of Rectal Balloon-filling Materials on the Dosimetry of Prostate and Organs at Risk in Photon Beam Therapy

Journal of Applied Clinical Medical Physics / American College of Medical Physics. 2013  |  Pubmed ID: 23318385

The use of rectal balloon in radiotherapy of prostate cancer is shown to be effective in reducing prostate motion and minimizing rectal volume, thus reducing rectal toxicity. Air-filled rectal balloon has been used most commonly, but creates dose perturbation at the air-tissue interface. In this study, we evaluate the effects of rectal balloon-filling materials on the dose distribution to the target and organs at risk. The dosimetric impact of rectal balloon filling was studied in detail for a typical prostate patient, and the general effect of the balloon filling was investigated from a study of ten prostate patients covering a wide range of anterior-posterior and left-right separations, as well as rectal and bladder volumes. Hounsfield units (HU) of the rectal balloon filling was changed from -1000 HU to 1000 HU at an interval of 250 HU, and the corresponding changes in the relative electron density (RED) was calculated. For each of the HU of the rectal balloon filling, a seven-field IMRT plan was generated with 6 MV and 15 MV photon beams, respectively. Dosimetric evaluation was performed with the AAA algorithm for inhomogeneity corrections. A detailed study of the rectal balloon filling shows that the GTV, PTV, rectal, and bladder mean dose decreased with increasing values of RED in the rectal balloon. There is significant underdosage in the target volume at the rectum-prostate interface with an air-filled balloon as compared to that with a water-filled balloon for both 6 MV and 15 MV beams. While the dosimetric effect of the rectal balloon filling is reduced when averaged over ten patients, generally an air-filled balloon results in lower minimum dose and lower mean dose in the overlap region (and possibly the PTV) compared to those produced by water-filled or contrast-filled balloons. Dose inhomogeneity in the target volume is increased with an air-filled rectal balloon. Thus a water-filled or contrast-filled rectal balloon is preferred to an air-filled rectal balloon in EBRT of prostate treatment.

The Translation Initiation Factor DAP5 Promotes IRES-driven Translation of P53 MRNA

Oncogene. Jan, 2013  |  Pubmed ID: 23318444

Translational regulation of the p53 mRNA can determine the ratio between p53 and its N-terminal truncated isoforms and therefore has a significant role in determining p53-regulated signaling pathways. Although its importance in cell fate decisions has been demonstrated repeatedly, little is known about the regulatory mechanisms that determine this ratio. Two internal ribosome entry sites (IRESs) residing within the 5'UTR and the coding sequence of p53 mRNA drive the translation of full-length p53 and Δ40p53 isoform, respectively. Here, we report that DAP5, a translation initiation factor shown to positively regulate the translation of various IRES containing mRNAs, promotes IRES-driven translation of p53 mRNA. Upon DAP5 depletion, p53 and Δ40p53 protein levels were decreased, with a greater effect on the N-terminal truncated isoform. Functional analysis using bicistronic vectors driving the expression of a reporter gene from each of these two IRESs indicated that DAP5 preferentially promotes translation from the second IRES residing in the coding sequence. Furthermore, p53 mRNA expressed from a plasmid carrying this second IRES was selectively shifted to lighter polysomes upon DAP5 knockdown. Consequently, Δ40p53 protein levels and the subsequent transcriptional activation of the 14-3-3σ gene, a known target of Δ40p53, were strongly reduced. In addition, we show here that DAP5 interacts with p53 IRES elements in in vitro and in vivo binding studies, proving for the first time that DAP5 directly binds a target mRNA. Thus, through its ability to regulate IRES-dependent translation of the p53 mRNA, DAP5 may control the ratio between different p53 isoforms encoded by a single mRNA.Oncogene advance online publication, 14 January 2013; doi:10.1038/onc.2012.626.

Engineered Andrographolide Nanoparticles Mitigate Paracetamol Hepatotoxicity in Mice

Pharmaceutical Research. Jan, 2013  |  Pubmed ID: 23319171

PURPOSE: Paracetamol (acetaminophen, APAP) overdose is often fatal due to progressive and irreversible hepatic necrosis. The aim of this work was to design Andrographolide (AG) loaded nanoparticles to prevent similar hepatic necrosis. METHODS: Functionalized AG-loaded PLGA nanoparticles carrying different densities of heparin were prepared following a facile emulsion solvent evaporation technique. Nanoparticle morphology, loading and release kinetics were studied. Hepatic localization of the nanoparticles was investigated in both normal and APAP damaged conditions using FITC fluorescent probe. Different serum parameters and liver histopathology were further examined as indicators of hepatic condition before and after treatment. RESULT: A collection of heparin functionalized AG-loaded PLGA nanoparticles were designed. Low amount of heparin on the particle surface could rapidly localize the nanoparticles up to the liver. The new functionalized AG nanoparticles affect efficient hepatoprotection in experimental mouse APAP overdose conditions. AG nanoparticle hepatoprotection was due to the rapid regeneration of antioxidant capacity and hepatic GSH store. CONCLUSIONS: Engineered nanoparticles loaded with AG provided a fast protection in APAP induced acute liver failure.

Predictors and Outcome of Hypoxemia in Severely Malnourished Children Under Five with Pneumonia: A Case Control Design

PloS One. 2013  |  Pubmed ID: 23320066

There is lack of information in the medical literature on predictors of hypoxemia in severely malnourished children with pneumonia, although hypoxemia is common and is often associated with fatal outcome in this population. We explored the predictors of hypoxemia in under-five children who were hospitalized for the management of pneumonia and severe acute malnutrition (SAM).

A Tri-atomic Renner-Teller System Entangled with Jahn-Teller Conical Intersections

The Journal of Chemical Physics. Jan, 2013  |  Pubmed ID: 23320674

The present study concentrates on a situation where a Renner-Teller (RT) system is entangled with Jahn-Teller (JT) conical intersections. Studies of this type were performed in the past for contours that surround the RT seam located along the collinear axis [see, for instance, G. J. Halász, Á. Vibók, R. Baer, and M. Baer, J. Chem. Phys. 125, 094102 (2006)]. The present study is characterized by planar contours that intersect the collinear axis, thus, forming a unique type of RT-non-adiabatic coupling terms (NACT) expressed in terms of Dirac-δ functions. Consequently, to calculate the required adiabatic-to-diabatic (mixing) angles, a new approach is developed. During this study we revealed the existence of a novel molecular parameter, η, which yields the coupling between the RT and the JT NACTs. This parameter was found to be a pure number η = 22/π (and therefore independent of any particular molecular system) and is designated as Renner-Jahn coupling parameter. The present study also reveals an unexpected result of the following kind: It is well known that each (complete) group of states, responsible for either the JT-effect or the RT-effect, forms a Hilbert space of its own. However, the entanglement between these two effects forms a third effect, namely, the RT∕JT effect and the states that take part in it form a different Hilbert space.

Indenoindolone Derivatives As Topoisomerase II-inhibiting Anticancer Agents

Bioorganic & Medicinal Chemistry Letters. Feb, 2013  |  Pubmed ID: 23321564

Based on known heterocyclic topoisomerase II inhibitors and anticancer agents, various indenoindolone derivatives were predicted as potential topoisomerase II-inhibiting anticancer agents. They are hydrazones, (thio)semicarbazones, and oximes of indenoindolones, and indenoindolols. These derivatives with suitable substitutions exhibited potent specific inhibition of human DNA TopoIIα while not showing inhibition of topoisomerase I and DNA intercalation, despite the fact that parent indenoindolones are known poor/moderate inhibitors of topoisomerase II. The potent topoisomerase II inhibitor indenoindolone derivatives exhibited good anticancer activities compared to etoposide and 5-fluorouracil, and relatively low toxicity to normal cells. These derivatizations of indenoindolones were found to result in enhancement of anticancer activities.

Isolation of a Novel Strain of Planomicrobium Chinense from Diesel Contaminated Soil of Tropical Environment

Journal of Basic Microbiology. Jan, 2013  |  Pubmed ID: 23322444

A novel bacterial strain (B6) degrading high concentration of diesel oil [up to 2.5% (v/v)] was isolated from a site contaminated with petroleum hydrocarbons in the state of Chhattisgarh, India. The strain demonstrated efficient degradation for diesel oil range alkanes (C(14) to C(36) i.e., mostly linear chain alkanes). It was identified to be 99% similar to Planomicrobium chinense on the basis of partial 16S rRNA gene sequencing and biochemical characteristics. The efficiency of degradation was optimized at pH 7.2 and temperature at 32 °C. GC analysis demonstrated complete mineralization of higher chain alkanes into lower chain alkanes within 96 h. The organism also displayed surface tension reduction by producing stable emulsification on the onset of stationary phase. A multidimensional characteristics of the strain to grow at a high temperature range, resistance to various heavy metals as well as tolerance to moderate concentration of NaCl makes it suitable for bioremediation of soil contaminated with diesel oil in tropical environment.

Optimization of Mechanical Ventilator Settings for Pulmonary Disease States

IEEE Transactions on Bio-medical Engineering. Jan, 2013  |  Pubmed ID: 23322759

The selection of mechanical ventilator settings that ensure adequate oxygenation and carbon dioxide clearance while minimizing the risk of ventilator-associated lung injury (VALI) is a significant challenge for intensive-care clinicians. Current guidelines are largely based on previous experience combined with recommendations from a limited number of in vivo studies whose data are typically more applicable to populations than to individuals suffering from particular diseases of the lung. By combining validated computational models of pulmonary pathophysiology with global optimization algorithms, we generate in silico experiments to examine current practice and uncover optimal combinations of ventilator settings for individual patient and disease states. Formulating the problem as a multiobjective, multivariable constrained optimization problem, we compute settings of tidal volume, ventilation rate, inspiratory/expiratory ratio, positive end-expiratory pressure and inspired fraction of oxygen that optimally manage the trade-offs between ensuring adequate oxygenation and carbon dioxide clearance and minimizing the risk of VALI for different pulmonary disease scenarios.

Dressed Adiabatic and Diabatic Potentials for the Renner-Teller/Jahn-Teller F + H(2) System

The Journal of Physical Chemistry. A. Jan, 2013  |  Pubmed ID: 23323799

We follow a suggestion by Lipoff and Herschbach ( Mol. Phys. 2010 , 108 , 1133 ) and compare dressed potentials to get insight regarding the low-energy dynamics (e.g., cold reaction) taking place in molecular systems. In this particular case we are interested in studying the effect of topological effects on the interacting atoms. For this purpose we consider dressed adiabatic and adiabatic-via-dressed diabatic potentials in the entrance channel of reactive systems. In a recent study of this kind for the F + H(2) system ( J. Chem. Phys. 2012 , 136 , 054104 ), we revealed that a single Jahn-Teller conical intersection is expected to have only a mild effect on the dynamics. This fact implies that the Born-Oppenheimer approximation is expected to be valid for this system at least for low enough energies. In the present article this study is extended to include also the Renner-Teller effect as produced by the two lower degenerate Π states. As a result we consider three electronic states which enforce the use of the adiabatic-to-diabatic transformation (ADT) matrix A. The results indicate that the topological effects as produced by the extended Renner/Teller-Jahn/Teller system are strong to the level that, most likely, abolishes the Born-Oppenheimer approximation for this system, all this in contrast to our previous findings (see above publication).

Late-Onset Sepsis in Very Low Birth Weight Infants from Singleton and Multiple-Gestation Births

The Journal of Pediatrics. Jan, 2013  |  Pubmed ID: 23324523

OBJECTIVES: To describe and compare the incidence of late-onset sepsis (LOS) and demographic and clinical characteristics associated with LOS in very low birth weight (VLBW) infants from singleton and multiple births, and to examine the heritability of susceptibility to LOS among VLBW twins by comparing same-sex and unlike-sex twin pairs. STUDY DESIGN: The study group comprised infants with birth weight 401-1500 g seen at clinical centers of the Eunice Kennedy Shriver National Institute of Child and Human Development Neonatal Research Network between 2002 and 2008. Only the first episode of LOS was included in our analysis. Stepwise logistic regression models were fitted separately for singleton and multiple pregnancies to examine the maternal and neonatal factors associated with LOS. LOS due solely to gram-negative bacteria in singleton and multiple pregnancies was also examined in separate models. The heritability of LOS was estimated by examining the concordance of LOS in twins from same-sex and unlike-sex pairs. RESULTS: LOS occurred in 25.0% (3797 of 15 178) of singleton and 22.6% (1196 of 5294) of multiple-birth VLBW infants. Coagulase-negative staphylococci were the most common infecting organisms, accounting for 53.2% of all LOS episodes in singletons and 49.2% in multiples. Escherichia coli and Klebsiella species were the most commonly isolated gram-negative organisms, and Candida albicans was the most commonly isolated fungus. Concordance of LOS did not differ significantly between same-sex and unlike-sex twin pairs. CONCLUSION: LOS remains a common problem in VLBW infants. The incidence of LOS is similar for singleton and multiple-birth infants. The similar concordance of LOS in same-sex and unlike-sex twin pairs provides no evidence that susceptibility to LOS among VLBW infants is genetically determined.

Advances in QSPR/QSTR Models of Ionic Liquids for the Design of Greener Solvents of the Future

Molecular Diversity. Feb, 2013  |  Pubmed ID: 23325356

In order to protect the life of all creatures living in the environment, the toxicity arising from various hazardous chemicals must be controlled. This imposes a serious responsibility on different chemical, pharmaceutical, and other biological industries to produce less harmful chemicals. Among various international initiatives on harmful aspects of chemicals, the 'Green Chemistry' ideology appears to be one of the most highlighted concepts that focus on the use of eco-friendly chemicals. Ionic liquids are a comparatively new addition to the huge garrison of chemical compounds released from the industry. Extensive research on ionic liquids in the past decade has shown them to be highly useful chemicals with a good degree of thermal and chemical stability, appreciable task specificity and minimal environmental release resulting in a notion of 'green chemical'. However, studies have also shown that ionic liquids are not intrinsically non-toxic agents and can pose severe degree of toxicity as well as the risk of bioaccumulation depending upon their structural components. Moreover, ionic liquids possess issues of waste generation during synthesis as well as separation problems. Predictive quantitative structure-activity relationship (QSAR) models constitute a rational opportunity to explore the structural attributes of ionic liquids towards various physicochemical and toxicological endpoints and thereby leading to the design of environmentally more benevolent analogues with higher process selectivity. Such studies on ionic liquids have been less extensive compared to other industrial chemicals. The present review attempts to summarize different QSAR studies performed on these chemicals and also highlights the safety, health and environmental issues along with the application specificity on the dogma of 'green chemistry'.

An Outbreak Investigation of Visceral Leishmaniasis Among Residents of Dharan Town, Eastern Nepal, Evidence for Urban Transmission of Leishmania Donovani

BMC Infectious Diseases. 2013  |  Pubmed ID: 23327548


A Case Series of NSCLC Patients with Different Molecular Characteristics and Choroidal Metastases: Improvement in Vision with Treatment Including Pemetrexed and Bevacizumab

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer. Feb, 2013  |  Pubmed ID: 23328555

Nanofiber-mediated Inhibition of Focal Adhesion Kinase Sensitizes Glioma Stemlike Cells to Epidermal Growth Factor Receptor Inhibition

Neuro-oncology. Jan, 2013  |  Pubmed ID: 23328812

BackgroundGlioblastoma multiforme is the most common glioma in adults and carries a poor prognosis, due to tumor recurrence despite aggressive treatment. Such relapse has been attributed to the persistence of glioma stemlike cells (GSCs), a subpopulation of glioma cells with stem cell properties. Thus, targeting these cells will be critical to achieving meaningful improvement in glioblastoma multiforme survival. We investigated the role of β1-integrin signaling as one such potential target.MethodsWe used GSCs isolated from primary human gliomas and maintained in stem cell conditions. We manipulated β1-integrin signaling using a self-assembling peptide amphiphile (PA) displaying the IKVAV (isoleucine-lysine-valine-alanine-valine) epitope as well as lentiviral overexpression, and we assayed the effects on downstream effectors and apoptosis using immunofluorescence.ResultsWe show that β1-integrin expression correlates with decreased survival in glioma patients and that β1-integrin is highly expressed by GSCs. The IKVAV PA potently increases immobilized β1-integrin at the GSC membrane, activating integrin-linked kinase while inhibiting focal adhesion kinase (FAK). The IKVAV PA induces striking apoptosis in GSCs via this FAK inhibition, which is enhanced in combination with inhibition of epidermal growth factor receptor (EGFR). Conversely, lentiviral overexpression of β1-integrin renders GSCs resistant to EGFR inhibition, which was overcome by FAK inhibition.ConclusionsThese observations reveal a role for β1-integrin signaling through FAK in GSC treatment resistance and introduce self-assembling PAs as a novel new therapeutic approach for overcoming this resistance.

Targeting RET to Induce Medullary Thyroid Cancer Cell Apoptosis: an Antagonistic Interplay Between PI3K/Akt and P38MAPK/caspase-8 Pathways

Apoptosis : an International Journal on Programmed Cell Death. Jan, 2013  |  Pubmed ID: 23329180

Mutations in REarranged during Transfection (RET) receptor tyrosine, followed by the oncogenic activation of RET kinase is responsible for the development of medullary thyroid carcinoma (MTC) that responds poorly to conventional chemotherapy. Targeting RET, therefore, might be useful in tailoring surveillance of MTC patients. Here we showed that theaflavins, the bioactive components of black tea, successfully induced apoptosis in human MTC cell line, TT, by inversely modulating two molecular pathways: (i) stalling PI3K/Akt/Bad pathway that resulted in mitochondrial transmembrane potential (MTP) loss, cytochrome-c release and activation of the executioner caspases-9 and -3, and (ii) upholding p38MAPK/caspase-8/caspase-3 pathway via inhibition of Ras/Raf/ERK. Over-expression of either constitutively active myristoylated-Akt-cDNA (Myr-Akt-cDNA) or dominant-negative-caspase-8-cDNA (Dn-caspase-8-cDNA) partially blocked theaflavin-induced apoptosis, while co-transfection of Myr-Akt-cDNA and Dn-caspase-8-cDNA completely eradicated the effect of theaflavins thereby negating the possibility of existence of other pathways. A search for the upstream signaling revealed that theaflavin-induced disruption of lipid raft caused interference in anchorage of RET in lipid raft that in turn stalled phosphorylation of Ras and PI3Kinase. In such anti-survival cellular micro-environment, pro-apoptotic signals were triggered to culminate into programmed death of MTC cell. These findings not only unveil a hitherto unexplained mechanism underlying theaflavin-induced MTC death, but also validate RET as a promising and potential target for MTC therapy.

Vitamin A Supplementation in Extremely Low-Birth-Weight Infants: Subgroup Analysis in Small-for-Gestational-Age Infants

American Journal of Perinatology. Jan, 2013  |  Pubmed ID: 23329565

Objective Preterm infants with intrauterine growth restriction are at increased risk of respiratory distress syndrome and bronchopulmonary dysplasia (BPD). A randomized clinical trial by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network demonstrated that vitamin A supplementation in extremely low-birth-weight (ELBW) preterm infants requiring early respiratory support decreased the risk of developing BPD.Study Design A subgroup analysis of small-for-gestational-age (SGA) infants from the original NICHD trial was performed to test the hypothesis that in infants requiring early respiratory support, vitamin A supplementation decreases the relative risk of BPD or death in premature SGA infants to a greater extent than in gestational age-equivalent vitamin A-treated appropriate-for-gestational-age (AGA) infants.Results Although vitamin A supplementation significantly increased serum retinol concentrations in AGA ELBW infants (median [5th percentile, 95th percentile]: 16.3 [-7.0, 68.8] versus 2.4 [-13.9, 55.1]; p < 0.001), no increases were noted in SGA ELBW infants.Conclusions Given the limited power of this analysis due to a low number of SGA infants, these data did not provide evidence to support the hypothesis that vitamin A supplementation in preterm SGA infants requiring early respiratory support decreases the relative risk of BPD or death as compared with preterm AGA infants.

Oxygen Switch in Visible-light Photoredox Catalysis: Radical Additions and Cyclizations and Unexpected C-C-bond Cleavage Reactions

Journal of the American Chemical Society. Feb, 2013  |  Pubmed ID: 23330701

Visible light photoredox catalyzed inter- and intramolecular C-H functionalization reactions of tertiary amines have been developed. Oxygen was found to act as chemical switch to trigger two different reaction pathways and to obtain two different types of products from the same starting material. In the absence of oxygen, the intermolecular addition of N,N-dimethyl-anilines to electron-deficient alkenes provided γ-amino nitriles in good to high yields. In the presence of oxygen, a radical addition/cyclization reaction occurred which resulted in the formation of tetrahydroquinoline derivatives in good yields under mild reaction conditions. The intramolecular version of the radical addition led to the unexpected formation of indole-3-carboxaldehyde derivatives. Mechanistic investigations of this reaction cascade uncovered a new photoredox catalyzed C-C bond cleavage reaction.

Interaction Between Group IIb Divalent Transition-Metal Cations and 3-Mercaptopropionic Acid: A Computational and Topological Perspective

The Journal of Physical Chemistry. A. Feb, 2013  |  Pubmed ID: 23330972

Density functional theory was applied to study the interaction of group IIb transition-metal cations (Zn(2+), Cd(2+), and Hg(2+)) with one and two fully or partially deprotonated 3-mercaptopropionic acid ligands. In this investigation, we determined the geometries of all possible complexes resulting from the coordination of the metal ions with the ligands at different binding sites selected on each ligand. The relative energies of the complexes, metal-ion affinities, free energies, and entropies were also determined. The natures of the bonds were critically analyzed by natural bond orbital (NBO) analysis and clarified further using the atoms-in-molecules (AIM) approach. The substantial influence of the solvent (water) polarization on the energetics, geometries, and bonding of the molecular complexes was also investigated by the conductor-like screening solvation model (COSMO). In an attempt to simulate the complexes in an aqueous environment, water molecules were added explicitly to complete the coordination sphere of the metal cations, and the corresponding metal-ion affinities were calculated to study the effect of microhydration.

Surface Passivation and Interface Properties of Bulk GaAs and Epitaxial-GaAs/Ge Using Atomic Layer Deposited TiAlO Alloy Dielectric

ACS Applied Materials & Interfaces. Jan, 2013  |  Pubmed ID: 23331503

High quality surface passivation on bulk-GaAs substrates and epitaxial-GaAs/Ge (epi-GaAs) layers were achieved by using atomic layer deposited (ALD) titanium aluminum oxide (TiAlO) alloy dielectric. The TiAlO alloy dielectric suppresses the formation of defective native oxide on GaAs layers. X-ray photoelectron spectroscopy (XPS) analysis shows interfacial arsenic oxide (As(x)O(y)) and elemental arsenic (As) were completely removed from the GaAs surface. Energy dispersive X-ray diffraction (EDX) analysis and secondary ion mass spectroscopy (SIMS) analysis showed that TiAlO dielectric is an effective barrier layer for reducing the out-diffusion of elemental atoms, enhancing the electrical properties of bulk-GaAs based metal-oxide-semiconductor (MOS) devices. Moreover, ALD TiAlO alloy dielectric on epi-GaAs with AlGaAs buffer layer realized smooth interface between epi-GaAs layers and TiAlO dielectric, yielding a high quality surface passivation on epi-GaAs layers, much sought-after for high-speed transistor applications on a silicon platform. Presence of a thin AlGaAs buffer layer between epi-GaAs and Ge substrates improved interface quality and gate dielectric quality through the reduction of interfacial layer formation (Ga(x)O(y)) and suppression of elemental out-diffusion (Ga and As). The AlGaAs buffer layer and TiAlO dielectric play a key role to suppress the roughening, interfacial layer formation, and impurity diffusion into the dielectric, which in turn largely enhances the electrical property of the epi-GaAs MOS devices.

Energy Transfer Ratio As a Metric of Right Ventricular Efficiency in Repaired Congenital Heart Disease

Congenital Heart Disease. Jan, 2013  |  Pubmed ID: 23331703

OBJECTIVE: With the success of early repair, continued functional assessment of repaired congenital heart disease is critical for improved long-term outcome. Pulmonary regurgitation, which is one of the main postoperative sequelae of congenital heart disease involved with the right ventricle (RV) such as tetralogy of Fallot and transposition of the great arteries, results in progressive RV dilatation coupled with pulmonary artery (PA) obstruction causing elevated RV pressures. The appropriate timing of intervention to correct these postoperative lesions remains largely subjective. In the present study, we evaluated an energy-based end point, namely energy transfer ratio (e(MPA) ), to assess the degree of RV and PA inefficiency in a group of congenital heart disease patients with abnormal RV-PA physiology. METHODS: Eight patients with abnormal RV-PA physiology and six controls with normal RV-PA physiology were investigated using a previously validated technique that couples cardiac magnetic resonance imaging and invasive pressure measurements. RESULTS: The mean e(MPA) of the patient group (0.56 ± 0.33) was significantly lower (P <.04) than that of the control group (1.56 ± 0.85), despite the fact that the patient group had a significantly higher RV stroke work indexed to body surface area (RV SW(I) ) than the control group (0.205 ± 0.095 J/m(2) vs. 0.090 ± 0.038 J/m(2) ; P <.02). CONCLUSION: We determined that the patients had inefficient RV-PA physiology due to a combination of RV dilatation with pulmonary regurgitation and RV outflow obstruction leading to an elevated end-systolic pressure. Using coupled magnetic resonance imaging and invasive pressure measurements, e(MPA) is determined to be a sensitive energy-based end point for measuring RV-PA efficiency. It may serve as a diagnostic end point to optimize timing of intervention.

Investigations of Dipeptide Structures Containing Pyrrolysine As N-terminal Residues: a DFT Study in Gas and Aqueous Phase

Journal of Molecular Modeling. Jan, 2013  |  Pubmed ID: 23334349

A set of six dipeptides containing pyrrolysine invariably at their N-terminal positions is studied in gas and aqueous phase using a polarizable continuum model (PCM). The molecular geometries of the dipeptides are fully optimized at B3LYP/6-31++G(d,p) level of theory and a second derivative (frequency) analysis confirms that all the optimized geometries are true minima. The effects of solvation and identity of the varying C-terminal residue on the energetics, structural features of the peptide planes, values of the ψ and ϕ dihedrals, geometry around the α-carbon atoms and theoretically predicted vibrational spectra of the dipeptides are thoroughly analyzed. Solvation effects are found to modify the gas phase conformation of the dipeptides around ψ dihedrals while the identity of the varying C-terminal residue affect the values of ϕ, planarity of the peptide planes and geometry around the α-carbon atoms. The presence or absence of three types of intramolecular H-bonds, namely O…H-N, N…H-N and O…H-C that leave noticeable signatures in the IR spectra, play crucial roles in influencing the geometry of the peptide planes and in determining the energetics of the dipeptides.

Overexpression of MicroRNA-122 Enhances in Vitro Hepatic Differentiation of Fetal Liver-derived Stem/progenitor Cells

Journal of Cellular Biochemistry. Jan, 2013  |  Pubmed ID: 23334867

MicroRNAs (miRNAs) are a versatile class of tiny non-coding RNAs involved in regulation of various biological processes. miRNA-122 (miR-122) is specifically and abundantly expressed in human liver. However, the role of miR-122 in differentiation of fetal liver stem/progenitor cells into hepatocytes remains unclear. In this study, dual positive CD34+/CD117+ expressing human fetal liver stem/progenitor cells was enriched by magnetic cell sorting and cultured in vitro. The level of miR-122 was found to be increased at specific time intervals. Interestingly, during the differentiation process of hepatocyte-like cells, the increase in expression of miR-122 was positively correlated with expression of hepatocyte-specific genes. The status of differentiation process was improved by transfection of miR-122 into enriched stem/progenitor cells. The expression level of hepatic-specific genes as well as liver-enriched transcription factors (LETFs) was significantly increased by overexpression of miR-122 in fetal liver stem/progenitor cells. Thus, the study delineated the role of hepato-specific miR-122 in differentiation of fetal liver stem/progenitor cells into hepatocyte-like cells which could be used as a therapeutic target molecule to generate abundant hepatocytes. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

Protective Effect of Ascorbic Acid Against Ethanol-induced Reproductive Toxicity in Male Guinea Pigs

The British Journal of Nutrition. Jan, 2013  |  Pubmed ID: 23336340

The present study was undertaken to elucidate the effect of ascorbic acid on alcohol-induced reproductive toxicity and also to compare it with that of abstention. A total of thirty-six male guinea pigs were divided into two groups and were maintained for 90 d as control and ethanol-treated groups (4 g/kg body weight (b.wt.)). After 90 d, ethanol administration was stopped and animals in the control group were divided into two groups and then maintained for 30 d as the control and control+ascorbic acid groups and those in the ethanol-treated group as ethanol abstention and ethanol+ascorbic acid (25 mg/100 g b. wt.) groups. Animals treated with ethanol showed a significant decline in sperm quality (P< 0·001), decreased activity of steroidogenic enzymes (P< 0·05) and reduced serum testosterone (P< 0·05), luteinising hormone and follicle-stimulating hormone levels, decrease in the activity of testicular succinate dehydrogenase, adenosine triphosphatase, sorbitol dehydrogenase and reduction in fructose content (P< 0·05). It also caused an increase in testicular malondialdehyde levels (P< 0·05) and decrease in the levels of glutathione content (P< 0·001) of testes. Ascorbic acid levels in testes and plasma were also reduced (P< 0·001) in ethanol-fed animals. Ascorbic acid supplementation altered all these parameters and produced a better and faster recovery from alcohol-induced reproductive toxicity than abstention. The mechanism of action of ascorbic acid may be by reducing the oxidative stress and improving antioxidant status, which eventually changed the microenvironment of testes and enhanced the energy needed for motility of sperms, improved the sperm morphology and elevated the testosterone and gonadotropin levels.

Solvation Dynamics of Biological Water in a Single Live Cell Under a Confocal Microscope

Langmuir : the ACS Journal of Surfaces and Colloids. Feb, 2013  |  Pubmed ID: 23336846

Time-resolved confocal microscopy has been applied to study the cytoplasm and nucleus region of a single live Chinese hamster ovary (CHO) cell. To select the cytoplasm and the nucleus region, two different fluorescent probes are used. A hydrophobic fluorescent dye, DCM, localizes preferentially in the cytoplasm region of a CHO cell. A DNA binding dye, DAPI, is found to be inside the nucleus of the cell. The locations of the probes are clearly seen in the image. Emission maxima of the dyes (DCM in cytoplasm and DAPI in the nucleus) are compared to those of the same dyes in different solvents. From this, it is concluded that the polarity (dielectric constant, ε) of the microenvironment of DCM in the cytoplasm is ∼15. The nucleus is found to be much more polar with ε ≈ 60 (as reported by DAPI). The diffusion coefficient (and hence viscosity) in the cytoplasm and the nucleus was determined using fluorescence correlation spectroscopy (FCS). The diffusion coefficient (D(t)) of the dye (DCM) in the cytoplasm is 2 μm(2) s(-1) and is ∼150 times slower than that in bulk water (buffer). D(t) of DAPI in the nucleus (15 μm(2) s(-1)) is 30 times slower than that in bulk water (buffer). The extremely slow diffusion inside the cell has been ascribed to higher viscosity and also to the binding of the probes (DCM and DAPI) to large biological macromolecules. The solvation dynamics of water in the cytoplasm (monitored by DCM) exhibits an average relaxation time ⟨τ(sol)⟩ of 1250 ± 50 ps, which is about 1000 times slower than in bulk water (1 ps). The solvation dynamics inside the nucleus (studied using DAPI) is about 2-fold faster, ⟨τ(sol)⟩ ≈ 775 ps. The higher polarity, faster diffusion, and faster solvation dynamics in the nucleus indicates that it is less crowded and less restricted than the cytoplasm.

The Prevalence of Bullying and Cyberbullying in High School: a 2011 Survey

International Journal of Adolescent Medicine and Health. Jan, 2013  |  Pubmed ID: 23337050

Abstract Background: Bullying is common among young students, and cyberbullying has increased due to the use of technology. This study investigates the prevalence of bullying and cyberbullying among high school students and the emotional effects of bullying on students. Methods: Students at East Chapel Hill High School, Chapel Hill, North Carolina completed the Gatehouse Bullying Scale and the Peer Relations Questionnaire. They answered questions regarding how often they had experienced certain types of bullying in school and the emotional effects the bullying had on them. Results: The combined results from both surveys indicated that the prevalence of bullying was 55% with 18% of respondents reporting cyberbullying. Teasing and name-calling were the most common types of bullying, as 40% of students reported having been teased or called names. The most serious type of bullying, being threatened with harm, hit, or kicked, occurred in 20% of boys and 8% of girls, with 25% of respondents reported "quite upset" by the experience. The majority (79%) of students who had been bullied did not share with anyone about being bullied, and of those who did, only 50% were taken seriously. Conclusions: Bullying is still prevalent among high school students, and cyberbullying is becoming more widespread. Most victims do not share their bullying experience, and if they did, only half believe they are taken seriously. Both bullying among students in school and cyberbullying deserve attention due to their potentially devastating effects on victims.

Inhibition of Leukemic U937 Cell Growth by Induction of Apoptosis, Cell Cycle Arrest and Suppression of VEGF, MMP-2 and MMP-9 Activities by Cytotoxin Protein NN-32 Purified from Indian Spectacled Cobra (Naja Naja) Venom

Toxicon : Official Journal of the International Society on Toxinology. Jan, 2013  |  Pubmed ID: 23337397

A cytotoxin NN-32 (6.7 kDa) from Indian cobra (Naja naja) venom inhibited human leukemic U937 cell growth as observed by Trypan blue dye exclusion method and cytotoxicity was confirmed by MTT assay. NN-32 induced apoptosis of U937 cell and cell cycle arrest of sub-G1 phase were revealed by FACS analysis. Increased Bax/Bcl-2 ratio, increased caspase 3 and 9 activities, cleaved PARP, decreased VEGF, MMP-2 and MMP-9 activities were observed after NN-32 treatment of U937 cell. Antileukemic activity of NN-32 on U937 cell may be due to activation of apoptosis, arresting cell cycle and antiangiogenesis activities.

Isolable, Copper(i) Dicarbonyl Complexes Supported by N-heterocyclic Carbenes

Inorganic Chemistry. Feb, 2013  |  Pubmed ID: 23339443

Cationic copper(I) dicarbonyl complexes supported by N-heterocyclic carbene ligands, SIPr and IPr*, have been synthesized. [(SIPr)Cu(CO)(2)][SbF(6)] and [(IPr*)Cu(CO)(2)][SbF(6)] have a trigonal planar, three-coordinate copper atom with an average Cu-CO distance of 1.915 Å and display C-O stretching frequencies higher than that of the free CO (2143 cm(-1)). The high CO stretching frequencies suggest that the Cu(I)-CO interaction in these cationic adducts is dominated by electrostatic and OC → Cu σ-donor components. [(SIPr)Cu(CO)(2)][SbF(6)] and [(IPr*)Cu(CO)(2)][SbF(6)] readily form the corresponding [(SIPr)Cu(CO)(H(2)O)][SbF(6)] and [(IPr*)Cu(CO)(H(2)O)][SbF(6)] with loss of a CO even with traces of water, but they can be converted back to the dicarbonyl adducts using excess CO. The synthesis and structure of [(IPr*)Cu(H(2)O)][SbF(6)] are also reported. It is a two-coordinate copper adduct with a Cu-O distance of 1.874(2) Å. It reacts with excess CO to form [(IPr*)Cu(CO)(2)][SbF(6)].

Bilateral Pleural Effusions in a 23-year-old Man: a Clinical Puzzle

QJM : Monthly Journal of the Association of Physicians. Jan, 2013  |  Pubmed ID: 23340389

Non-uniform Membrane Diffusion Enables Steady-state Cell Polarization Via Vesicular Trafficking

Nature Communications. Jan, 2013  |  Pubmed ID: 23340420

Actin-based vesicular trafficking of Cdc42, leading to a polarized concentration of the GTPase, has been implicated in cell polarization, but it was recently debated whether this mechanism allows stable maintenance of cell polarity. Here we show that endocytosis and exocytosis are spatially segregated in the polar plasma membrane, with sites of exocytosis correlating with microdomains of higher concentration and slower diffusion of Cdc42 compared with surrounding regions. Numerical simulations using experimentally obtained diffusion coefficients and trafficking geometry revealed that non-uniform membrane diffusion of Cdc42 in fact enables temporally sustained cell polarity. We show further that phosphatidylserine, a phospholipid recently found to be crucial for cell polarity, is enriched in Cdc42 microdomains. Weakening a potential interaction between phosphatidylserine and Cdc42 enhances Cdc42 diffusion in the microdomains but impedes the strength of polarization. These findings demonstrate a critical role for membrane microdomains in vesicular trafficking-mediated cell polarity.

PVP Stabilized Pt Nano Particles Catalyzed De-oxygenation of Phenoxazine Group by Hydrazine in Physiological Buffer Media: Surfactant Competes with Reactants for the Same Surface Sites

Dalton Transactions (Cambridge, England : 2003). Jan, 2013  |  Pubmed ID: 23340587

PVP capped platinum nano particles (PNP) of 5 nm diameter were prepared and characterized as homogeneous and of spherical nature. At physiological pH range (6.0-8.0), these PNP catalyze the deoxygenation of phenoxazine group containing resazurin () by hydrazine. The observed rate constants (k(o)), increase linearly with [PNP] at constant [] and [Hydrazine]; but first increase and then after reaching a maximum it decrease with increase in [] as well as in [Hydrazine]. The k(o) values increase linearly with /[H(+)] indicating N(2)H(4) as the reducing species that generates from the PNP assisted deprotonation of N(2)H(5)(+). The kinetic observations suggest Langmuir-Hinshelwood type surface reaction mechanism where both and hydrazine are adsorbed on nano particles surface and compete for the same sites. Interestingly, the surfactant molecules, polyvinylpyrrolidone (PVP), though do not take part into reduction reaction but having same type of functional groups as reactants, competes with them for the same surface sites. Adsorption on PNP with same type of functional group is further supported by the FTIR spectra of Pt-PVP and Pt-. Thus on increasing [PVP], k(o) decreases linearly and only when [PVP] is held constant, the plot of k(o)vs. [PNP] passes through the origin indicating the insignificance of uncatalyzed reaction. The plot of ln k(o)vs. [] or [Hydrazine] shows two different linear zones with different exponent values with respect to [] and [Hydrazine]. This indicates that along with the complex heterogeneous surface adsorption processes, the mutual interactions between the reactants are also changing with the relative concentrations of reactants or, in general, with the molar ratio ([Hydrazine]/[]).

Metabolite Profiles in the Anterior Cingulate Cortex of Depressed Patients Differentiate Those Taking N-acetyl-cysteine Versus Placebo

The Australian and New Zealand Journal of Psychiatry. Jan, 2013  |  Pubmed ID: 23341476

Background:Increased oxidative stress is thought to contribute to the pathophysiology of major depressive disorder (MDD), which is in part due to diminished levels of glutathione, the primary anti-oxidant of the brain. Oral administration of N-acetyl-cysteine (NAC) replenishes glutathione and has therefore been shown to reduce depressive symptoms. Proton magnetic spectroscopy ((1)H-MRS) that allows quantification of brain metabolites pertinent to both MDD and oxidative biology may provide some novel insights into the neurobiological effects of NAC, and in particular metabolite concentrations within the anterior cingulate cortex (ACC) are likely to be important given the key role of this region in the regulation of affect.Objective:The aim of this study was to determine whether the metabolite profile of the ACC in MDD patients predicts treatment with adjunctive NAC versus placebo.Methods:This study was nested within a multicentre, randomized, double-blind, placebo-controlled study of MDD participants treated with adjunctive NAC. Participants (n = 76) from one site completed the spectroscopy component at the end of treatment (12 weeks). Spectra from a single-voxel in the ACC were acquired and absolute concentrations of glutamate (Glu), glutamate-glutamine (Glx), N-acetyl-aspartate (NAA) and myo-inositol (mI) were obtained. Binary logistic regression analysis was performed to determine whether metabolite profiles could predict NAC versus placebo group membership.Results:When predicting group outcome (NAC or placebo), Glx, NAA and mI were a significant model, and had 75% accuracy, while controlling for depression severity and sex. However, the Glu, NAA and mI profile was only predictive at a trend level, with 68.3% accuracy. For both models, the log of the odds of a participant being in the NAC group was positively related to NAA, Glx and Glu levels and negatively related to mI levels.Conclusion:The finding of higher Glx and NAA levels being predictive of the NAC group provides preliminary support for the putative anti-oxidative role of NAC in MDD.

Monoclonal Antibodies Against Hepatitis C Genotype 3a Virus Like Particle Inhibit Virus Entry in Cell Culture System

PloS One. 2013  |  Pubmed ID: 23341957

The envelope protein (E1-E2) of Hepatitis C virus (HCV) is a major component of the viral structure. The glycosylated envelope protein is considered to be important for initiation of infection by binding to cellular receptor(s) and also known as one of the major antigenic targets to host immune response. The present study was aimed at identifying mouse monoclonal antibodies which inhibit binding of virus like particles of HCV to target cells. The first step in this direction was to generate recombinant HCV-like particles (HCV-LPs) specific for genotypes 3a of HCV (prevalent in India) using the genes encoding core, E1 and E2 envelop proteins in a baculovirus expression system. The purified HCV-LPs were characterized by ELISA and electron microscopy and were used to generate monoclonal antibodies (mAbs) in mice. Two monoclonal antibodies (E8G9 and H1H10) specific for the E2 region of envelope protein of HCV genotype 3a, were found to reduce the virus binding to Huh7 cells. However, the mAbs generated against HCV genotype 1b (D2H3, G2C7, E1B11) were not so effective. More importantly, mAb E8G9 showed significant inhibition of the virus entry in HCV JFH1 cell culture system. Finally, the epitopic regions on E2 protein which bind to the mAbs have also been identified. Results suggest a new therapeutic strategy and provide the proof of concept that mAb against HCV-LP could be effective in preventing virus entry into liver cells to block HCV replication.

Detecting Allosteric Sites of HIV-1 Reverse Transcriptase by X-ray Crystallographic Fragment Screening

Journal of Medicinal Chemistry. Jan, 2013  |  Pubmed ID: 23342998

HIV-1 reverse transcriptase (RT) plays an essential role in viral replication and is an attractive target for antiretroviral therapy. RT, a p66/p51 heterodimer, is a multi-domain protein that undergoes a series of conformational changes during the replication of the HIV-1 genome. The intrinsic flexibility of RT can provide novel allosteric sites for inhibition. Crystals of RT that diffract X-rays to better than 2 Ã… resolution facilitated the probing of RT for new druggable sites using X-ray crystallographic fragment screening. A total of 775 fragments were grouped into 143 cocktails, which were soaked into crystals of RT in complex with the non-nucleoside drug Edurant (TMC278/rilpivirine). Fragment binding was observed at seven new binding sites. These include the incoming nucleotide binding, Knuckles, NNRTI Adjacent, and 399 sites, located in the polymerase region of RT, and the 428, RNase H primer grip adjacent, and 507 sites, located in the RNase H region. Three of these sites-Knuckles, NNRTI adjacent, and the incoming nucleotide binding-are inhibitory and provide opportunities for discovery of new anti-AIDS drugs.

Major Histocompatibility Complex Class I and II Expression in Idiopathic Inflammatory Myopathy

Applied Immunohistochemistry & Molecular Morphology : AIMM / Official Publication of the Society for Applied Immunohistochemistry. Jan, 2013  |  Pubmed ID: 23343957

INTRODUCTION:: We sought to study the intensity and pattern of major histocompatibility complex (MHC) I and II expression in muscle from patients with biopsy-proven idiopathic inflammatory myositis (IIM) including the subgroups, polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM). METHODS:: A total of 120 muscle biopsies (61 PM, 14 DM, and 45 IBM) were immunostained for MHC I and II. Staining was graded as follows. 0: no staining, 1+: ≤10% fibers, 2+: 10% to 25%, 3+: 25% to 50%, 4+: 50% to 99%, and 5+ 100%. RESULTS:: All IIM biopsies showed MHC I positivity; 93% showed MHC II positivity. The proportion of patients with MHC II score ≥3+ was higher in IBM than DM or PM. In DM, MHC I expression showed a perifascicular pattern. All IBM biopsies were immunopositive for MHC I and II; 30/45 were scored 5+. DISCUSSION:: Immunostaining for MHC I and II is a useful adjunctive test in diagnosis and subclassification of IIM.

Pleural Tuberculosis Following Lung Cancer Chemotherapy: a Report of Two Cases Proven Pathologically by Pleural Biopsy

BMJ Case Reports. 2013  |  Pubmed ID: 23345502

Malignancy per se and cytotoxic chemotherapy given for its treatment both are recognised risk factors for the development of tuberculosis (TB). However, individual case descriptions of pleural tuberculosis (TB-PE) following chemotherapy for lung cancer (LC) have not been published previously. We herein report the first two cases of histopathologically proven TB-PE following LC chemotherapy. The first patient was a 38-year-old man with stage IV non-small cell LC (adenocarcinoma) who developed TB-PE following four cycles of chemotherapy (pemetrexed-cisplatin). The second patient was a 49-year-old man with extensive disease small cell LC who developed TB-PE after six cycles of chemotherapy (irinotecan-cisplatin). In both patients, diagnosis of TB-PE was established by demonstration of granulomatous inflammation, caseous necrosis and positive stain for acid-fast bacilli in pleural biopsy specimens. Both cases responded to standard four-drug antitubercular therapy. These cases highlight the importance of carrying out an extensive evaluation for exudative pleural effusions in LC patients receiving chemotherapy, especially in countries with high TB prevalence. Attributing such pleural effusions to disease progression, without histopathological confirmation, may be associated with disastrous consequences.

Effect of Concentrate Supplementation on Feed Consumption, Nutrient Utilization and Blood Metabolite Profile in Captive Spotted Deer (Axis Axis) Fed Oat (Avena Sativa) and Berseem (Trifolium Alexandrinum) Fodders Based Diet

Zoo Biology. Jan, 2013  |  Pubmed ID: 23349033

This experiment was conducted to determine the optimum level of a maize-soybean meal-wheat bran concentrate supplement fed to captive spotted deer fed an oat and berseem fodder-based diet. Twelve adult spotted deer [64-76 kg body weight (BW)] were distributed into three groups of four each and were housed individually. A diet consisting of 5 kg of oat fodder and 5.5 kg of berseem fodder was offered to each one of the experimental animals. The animal in group I received no supplementary concentrate, whereas, those in groups II and III received 0.5 and 1 kg of supplementary concentrate, respectively. A 60 days digestibility trial was conducted with a 5 days collection period on Days 55-59 of the trial. Blood samples were collected from all animals on Day 60 of the experiment. Average daily dry matter intake (DMI) was 1,224, 1,613, and 1,574 g/day in groups I, II, and III, respectively. Dry matter (DM) and organic matter (OM) intake was lowest (P < 0.01) in group I. Intake of P, Cu, and Zn was highest (P < 0.01) in group III, followed by groups II and I. Digestibility of neutral detergent fiber was highest (P < 0.05) in group II. Digestibility of OM and CP was lowest (P < 0.05) in group I. Digestibility of gross energy was highest (P < 0.01) in group III (74.9%), followed by groups II (69.3%) and I (66.2%). Digestible energy (DE) intake (kcal/kg BW(0.75) ) was highest (P < 0.01) in group III (195.4), followed by groups II (180.9) and I (129.8). Initial BW was 72.7, 72.5, and 71.0 kg, whereas, final BW was 71.0, 72.7, and 73.5 kg, in groups I, II and III, respectively. Average daily change in body mass was significantly (P < 0.01) different among the groups. The body mass was lost (-29.2 g/day), maintained (4.1 g/day) and gained (41.6 g/day) in groups I, II, and III, respectively. Blood glucose and cholesterol concentration was highest (P < 0.05) in group III, followed by groups II and I. Serum concentration of Cu and Zn was highest (P < 0.05) in group III, followed by groups II and I. Supplementation of forage only diet with 0.5 kg of concentrate mixture increased intake and digestibility of nutrients, without change in body mass. Animals fed 1 kg of supplementary concentrate received energy in excess of requirements, were consistently gaining body mass and were prone to obesity. Thus, it is a right strategy to supplement forage only diet of captive spotted deer with 0.5 kg of concentrate. Zoo Biol. XX:XX-XX, 2013. © 2013 Wiley Periodicals Inc.

Characterization of Nucleolin K88 Acetylation Defines a New Pool of Nucleolin Colocalizing with Pre-mRNA Splicing Factors

FEBS Letters. Jan, 2013  |  Pubmed ID: 23353999

Nucleolin is a multifunctional protein that carries several post-translational modifications. We characterized nucleolin acetylation and developed antibodies specific to nucleolin K88 acetylation. Using this antibody we show that nucleolin is acetylated in vivo and is not localized in the nucleoli, but instead is distributed throughout the nucleoplasm. Immunofluorescence studies indicate that acetylated nucleolin is co-localized with the splicing factor SC35 and partially with Y12. Acetylated nucleolin is expressed in all tested proliferating cell types. Our findings show that acetylation defines a new pool of nucleolin which support a role for nucleolin in the regulation of mRNA maturation and transcription by RNA polymerase II. STRUCTURED SUMMARY OF PROTEIN INTERACTIONS: SC35physically interacts with Nucleolin by anti bait coimmunoprecipitation (View interaction) Nucleolin and SC35colocalize by fluorescence microscopy (View interaction).

Biochemical Evaluation of Triploid Progenies of Diploid × Tetraploid Breeding Populations of Camellia for Genotypes Rich in Catechin and Caffeine

Biochemical Genetics. Jan, 2013  |  Pubmed ID: 23355000

To verify the quality of triploid varieties of Camellia tea species at the secondary metabolite level, we tested caffeine and catechin profiles of 97 F(1) segregating progenies in two breeding populations with a common tetraploid parent and diploid parents of two geographic and varietal origins. Catechin and caffeine levels of the triploid progenies were quantified and compared against their diploid parent. Some of the progenies showed better performance than their diploid parent. Most of the progenies of the diploid C. sinensis × tetraploid cross showed heterosis for caffeine and EGCG. Progenies of the C. assamica subsp. lasiocalyx × tetraploid cross showed heterosis for +C, EC, EGC, and TC. The genomic contributions of the diploid parent seem to be the main factor in the variation between the two populations. Our studies showed quantitative enhancement of some of the quality-related parameters in tea, providing a platform to refocus on this classical breeding approach for developing quality cultivars in tea.

Retention of Power Conversion Efficiency - from Small Area to Large Area Polymer Solar Cells

Advanced Materials (Deerfield Beach, Fla.). Jan, 2013  |  Pubmed ID: 23355271

A light harvesting device geometry is implemented for polymer solar cells that retain efficiency when the device area is scaled up. Patterning devices and incorporating suitable fluorescent dye doped polymers in the spaces between the patterns leads to 12% efficiency enhancement. Vacuum free deposition of electrodes is carried out using meltable alloys giving rise to device efficiency of 6%. The fluorescent layer along with the electrode serves as an active encapsulant leading to improved device stability.

The Effect of Including the C2 Insert of Nonmuscle Myosin II-C on Neuritogenesis

The Journal of Biological Chemistry. Jan, 2013  |  Pubmed ID: 23355468

The functional role of the C2 insert of nonmuscle myosin II-C (NM II-C) is poorly understood. Here, we report for the first time that the expression of the C2 insert containing isoform, NM II-C1C2 is inducible in Neuro-2a cells during differentiation both at mRNA and protein levels. Immunoblot and RT-PCR analysis reveal that expression of NM II-C1C2 peaks between days 3-6 of differentiation. Localization of NM II-C1C2 in Neuro-2a cells suggest that the C2 insert containing isoform is localized in the cytosol and along the neurites, specifically at adherance point to substratum. Inhibition of endogenous NM II-C1C2 using siRNA decreases the neurite length by 43% compared with control cells treated with nonspecific siRNA. Time lapse image analysis reveals that neurites of C2-siRNA treated cells have a net negative change in neurite length per minute, leading to a reduction of overall neurite length. During neuritogenesis, NM II-C1C2 can interact and colocalize with β1-integrin in neurites. Altogether, these studies indicate that NM II-C1C2 may be involved in stabilizing neurites by maintaining their structure at adhesion sites.

Prevalence and Medical Risks of Body Packing in the Amsterdam Area

Journal of Forensic and Legal Medicine. Feb, 2013  |  Pubmed ID: 23357392

Body packing is a way to deliver packets of drugs across international borders by ingestion. The aim of the study was to provide an estimate of the medical risks of body packing, describe predictors for hospital referral in detained body packers and provide an estimate for the prevalence of body packing in the Amsterdam area.

Non-Typhoidal Salmonella Gastroenteritis at a Diarrheal Hospital in Dhaka, Bangladesh, 1996-2011

The American Journal of Tropical Medicine and Hygiene. Jan, 2013  |  Pubmed ID: 23358644

Data on non-typhoidal Salmonella (NTS) infection in South Asia are limited. We used data gathered prospectively from 1996 to 2011 as part of a hospital surveillance system in Dhaka, Bangladesh, to identify diarrheal patients with NTS isolated from stool. NTS was isolated in 1.3% (468 of 37,439) of diarrheal patients; 47% of total cases of NTS were in children < 5 years of age, although older adults (≥ 60 years) had the highest isolation rates. NTS isolation peaked in the monsoon months of July and August. Over the study period, rates of multidrug resistance decreased, whereas rates of decreased susceptibility to ciprofloxacin increased. Compared with control patients, NTS patients were older and wealthier; however, no differences in type of housing or exposure to animals were found. NTS patients had increased inflammatory cells in stool and required more fluid resuscitation.

PH Dependent Multifunctional and Multiply-configurable Logic Gate Systems Based on Small Molecule G-quadruplex DNA Recognition

Chemical Communications (Cambridge, England). Feb, 2013  |  Pubmed ID: 23358682

A variety of logic operations such as XNOR, NOR, AND, NAND, NOT have been designed with pH as an external modulator by choosing thiazole orange (TO) and a c-kit2 promoter quadruplex as two inputs and fluorescence signals of pyridyl bis-indole amide (PBIA) and TO as two outputs.

Beam Angle Selection for Intensity-modulated Radiotherapy (IMRT) Treatment of Unresectable Pancreatic Cancer: Are Noncoplanar Beam Angles Necessary?

Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. Jan, 2013  |  Pubmed ID: 23359183

BACKGROUND AND PURPOSE: External beam radiation therapy with concurrent chemotherapy (CRT) is widely used for the treatment of unresectable pancreatic cancer. Noncoplanar (NCP) 3D conformal radiotherapy (3DCRT) and coplanar (CP) IMRT have been reported to lower the radiation dose to organs at risk (OARs). The purpose of this article is to examine the utility of noncoplanar beam angles in IMRT for the management of pancreatic cancer. MATERIALS AND METHODS: Sixteen patients who were treated with CRT for unresectable adenocarcinoma of the pancreatic head or neck were re-planned using CP and NCP beams in 3DCRT and IMRT with the Varian Eclipse treatment planning system. RESULTS: Compared to CP IMRT, NCP IMRT had similar target coverage with slightly increased maximum point dose, 5,799 versus 5,775 cGy (p = 0.008). NCP IMRT resulted in lower mean kidney dose, 787 versus 1,210 cGy (p < 0.0001) and higher mean liver dose, 1,208 versus 1,061 cGy (p < 0.0001). Also, NCP IMRT resulted in similar mean stomach dose, 1,257 versus 1,248 cGy (p = 0.86) but slightly higher mean small bowel dose, 981 versus 866 cGy (p < 0.0001). CONCLUSIONS: The NCP IMRT was able to significantly decrease bilateral kidney dose, but did not improve other dose-volume criteria. The use of NCP beam angles is preferred only in patients with risk factors for treatment-related kidney dysfunction.

Influence of Array Interspacing on the Force Required for Successful Microneedle Skin Penetration: Theoretical and Practical Approaches

Journal of Pharmaceutical Sciences. Jan, 2013  |  Pubmed ID: 23359221

Insertion behaviour of microneedle (MN) arrays depends upon the mechanical properties of the skin and, MN geometry and distribution in an array. In addressing this issue, this paper studies MN array insertion mechanism into skin and provides a simple quantitative basis to relate the insertion force with distance between two MNs. The presented framework is based on drawing an analogy between a beam on an elastic foundation and mechanism of needle insertion, where insertion force is separated into different components. A theoretical analysis indicates that insertion force decreases as interspacing increases. For a specified skin type, insertion force decreased from 0.029 to 0.028 N/MN when interspacing at MN tip was increased from 50 μm (350 μm at MN base) to 150 μm (450 μm at MN base). However, dependence of insertion force seems to decrease as the interspacing is increased beyond 150 μm. To assess the validity of the proposed model, a series of experiments was carried out to determine the force required for skin insertion of MN. Experiments performed at insertion speed of 0.5 and 1.0 mm/s yielded insertion force values of 0.030 and 0.0216 N, respectively, for 30 μm interspacing at MN base (330 μm interspacing at tip) and 0.028 and 0.0214 N, respectively, for 600 μm interspacing at MN base (900 μm interspacing at tip). Results from theoretical analysis and finite element modelling agree well with experimental results, which show MN interspacing only begins to affect insertion force at low interspacing (<150 μm interspacing at MN base). This model provides a framework for optimising MN devices, and should aid development of suitable application method and determination of force for reliable insertion into skin. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.

TGFβ-induced PI 3 Kinase-dependent MNK-1 Activation is Necessary for Ser-209 Phosphorylation of EIF4E and Mesangial Cell Hypertrophy

Journal of Cellular Physiology. Jan, 2013  |  Pubmed ID: 23359369

Transforming growth factorβ (TGFβ)-induced canonical signal transduction is involved in glomerular mesangial cell hypertrophy; however, the role played by the noncanonical TGFβ signaling remains largely unexplored. TGFβ time-dependently stimulated eIF4E phosphorylation at Ser-209 concomitant with enhanced phosphorylation of Erk1/2 (extracellular signal regulated kinase1/2) and MEK (mitogen-activated and extracellular signal-regulated kinase kinase) in mesangial cells. Inhibition of Erk1/2 by MEK inhibitor or by expression of dominant negative Erk2 blocked eIF4E phosphorylation, resulting in attenuation of TGFβ-induced protein synthesis and mesangial cell hypertrophy. Expression of constitutively active MEK was sufficient to induce protein synthesis and hypertrophy similar to those induced by TGFβ. Pharmacological or dominant negative inhibition of phosphatidylinositol (PI) 3 kinase decreased MEK/Erk1/2 phosphorylation leading to suppression of eIF4E phosphorylation. Inducible phosphorylation of eIF4E at Ser-209 is mediated by Mnk-1 (mitogen-activated protein kinase signal-integrating kinase-1). Both PI 3 kinase and Erk1/2 promoted phosphorylation of Mnk-1 in response to TGFβ. Dominant negative Mnk-1 significantly inhibited TGFβ-stimulated protein synthesis and hypertrophy. Interestingly, inhibition of mTORC1 activity, which blocks dissociation of eIF4E-4EBP-1 complex, decreased TGFβ-stimulated phosphorylation of eIF4E without any effect on Mnk-1 phosphorylation. Furthermore, mutant eIF4E S209D, which mimics phosphorylated eIF4E, promoted protein synthesis and hypertrophy similar to TGFβ. These results were confirmed using phosphorylation deficient mutant of eIF4E. Together our results highlight a significant role of dissociation of 4EBP-1-eIF4E complex for Mnk-1-mediated phosphorylation of eIF4E. Moreover, we conclude that TGFβ-induced noncanonical signaling circuit involving PI 3 kinase-dependent Mnk-1-mediated phosphorylation of eIF4E at Ser-209 is required to facilitate mesangial cell hypertrophy. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.

Community Perceptions on Malaria and Care-seeking Practices in Endemic Indian Settings: Policy Implications for the Malaria Control Programme

Malaria Journal. Jan, 2013  |  Pubmed ID: 23360508

ABSTRACT: BACKGROUND: The focus of India's National Malaria Programme witnessed a paradigm shift recently from health facility to community-based approaches. The current thrust is on diagnosing and treating malaria by community health workers and prevention through free provision of long-lasting insecticidal nets. However, appropriate community awareness and practice are inevitable for the effectiveness of such efforts. In this context, the study assessed community perceptions and practice on malaria and similar febrile illnesses. This evidence base is intended to direct the roll-out of the new strategies and improve community acceptance and utilization of services. METHODS: A qualitative study involving 26 focus group discussions and 40 key informant interviews was conducted in two districts of Odisha State in India. The key points of discussion were centred on community perceptions and practice regarding malaria prevention and treatment. Thematic analysis of data was performed. RESULTS: The 272 respondents consisted of 50% females, three-quarter scheduled tribe community and 30% students. A half of them were literates. Malaria was reported to be the most common disease in their settings with multiple modes of transmission by the FGD participants. Adoption of prevention methods was seasonal with perceived mosquito density. The reported use of bed nets was low and the utilization was determined by seasonality, affordability, intoxication and alternate uses of nets. Although respondents were aware of malaria-related symptoms, care-seeking from traditional healers and unqualified providers was prevalent. The respondents expressed lack of trust in the community health workers due to frequent drug stock-outs. The major determinants of health care seeking were socio-cultural beliefs, age, gender, faith in the service provider, proximity, poverty, and perceived effectiveness of available services. CONCLUSION: Apart from the socio-cultural and behavioural factors, the availability of acceptable care can modulate the community perceptions and practices on malaria management. The current community awareness on symptoms of malaria and prevention is fair, yet the prevention and treatment practices are not optimal. Promoting active community involvement and ownership in malaria control and management through strengthening community based organizations would be relevant. Further, the timely availability of drugs and commodities at the community level can improve their confidence in the public health system.

X-ray Absorption Spectroscopy and Energy Storage of Ni-doped Cobalt Nitride, (Ni(0.33)Co(0.67))N, Prepared by a Simple Synthesis Route

Nanoscale. Jan, 2013  |  Pubmed ID: 23360912

Metal nitride (Ni(0.33)Co(0.67))N nanoparticles are prepared by nitridation using NiCo(2)O(4) as a precursor material by heating at 335 °C for 2 h in flowing NH(3) + N(2) gas and characterized by X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), high resolution-transmission electron microscopy (HR-TEM), along with selective area electron diffraction (SAED) and X-ray absorption spectroscopy (XAS) techniques. The X-ray absorption near edge structure (XANES) at the Co K-edge showed that the oxidation state of cobalt is close to 3+. The (Ni(0.33)Co(0.67))N showed a shift in edge energy towards lower values due to Ni-doping to cobalt site. The Li-storage behaviour of (Ni(0.33)Co(0.67))N nanoparticles was evaluated by galvanostatic cycling and cyclic voltammetry in the cells with Li-metal as counter electrode in the voltage range of 0.005-3.0 V at ambient temperature. When cycled at 250 mA g(-1), the first-cycle reversible capacity of 700 (±5) mA h g(-1) (∼1.9 moles of Li) is obtained. It showed an initial decrease in capacity until the 10(th) cycle and a stable capacity of 400 (±5) mA h g(-1) (∼1.09 moles of Li) is observed at the end of the 50(th) cycle. Excellent rate capability is also shown when cycling at 500 mA g(-1) (up to 50 cycles). The materials showed excellent Li-ion insertion/extraction, with the coulombic efficiency reaching almost 99% in the range of 10-50 cycles. The average charge and discharge potentials are ∼2.03 and ∼1.0 V, respectively for the decomposition/formation of Li(3)N as determined by electroanalytical techniques.

High-Voltage Suicidal Electrocution With Multiple Exit Wounds

The American Journal of Forensic Medicine and Pathology. Jan, 2013  |  Pubmed ID: 23361081

ABSTRACT: Poisoning, hanging, and burning are the usual methods adopted by people to commit suicide. Suicide by electrocution and that too high voltage is one of the rarest methods adopted for the purpose. We report the case of a young man who committed suicide by climbing up a 25-ft-high electric pole. The deceased was a regular alcoholic and was under severe depression for a long time because of his personal problems. He survived for more than 2 days after the incident. His serum urea and creatinine levels were elevated, so were the creatine kinase total and creatine kinase-MB level. The method adopted and the findings make this case a rare scientific report. Moreover, to the best of our knowledge, this is the first reported case in an English scientific literature of a high-voltage suicidal electrocution with multiple exit wounds. The circumstances surrounding the manner of electrocution and the features of electric injuries are presented and discussed.

TGFβ Integrates SMAD 3 to Mechanistic Target of Rapamycin Complexes to Arrest Deptor Abundance for Glomerular Mesangial Cell Hypertrophy

The Journal of Biological Chemistry. Jan, 2013  |  Pubmed ID: 23362262

In many renal diseases, TGFβ-stimulated canonical Smad 3 and noncanonical mTOR promote increased protein synthesis and mesangial cell hypertrophy. The cellular underpinnings involving these signaling molecules to regulate mesangial cell hypertrophy are not fully understood. Deptor has recently been identified as an mTOR interacting protein and functions as an endogenous inhibitor of the kinase activity for both TORC1 and TORC2. Prolonged incubation of mesangial cells with TGFβ reduced the levels of deptor concomitant with increase in TORC1 and TORC2 activity. Sustained TGFβ activation was required to inhibit association of deptor with mTOR while rapid activation had no effect. Using mTOR inhibitor PP242, we found that TGFβ-induced both early and sustained activation of TORC1 and TORC2 were necessary for deptor suppression. PP242-induced reversal of deptor suppression by TGFβ was associated with significant inhibition of TGFβ-stimulated protein synthesis and hypertrophy. Interestingly, expression of siRNA against Smad 3 or Smad 7, which blocks TGFβ receptor-specific Smad 3 signaling, prevented TGFβ-induced suppression of deptor abundance and TORC1/2 activities. Furthermore, overexpression of Smad 3 decreased deptor expression similar to TGFβ stimulation concomitant with increased TORC1 and TORC2 activities. Finally, knockdown of deptor reversed Smad 7-mediated inhibition of protein synthesis and mesangial cell hypertrophy induced by TGFβ. These data reveal the requirement of both early and late activation of mTOR for TGFβ-induced protein synthesis. Our results support that TGFβ-stimulated Smad 3 acts as a key node to instill a feed back loop between deptor downregulation and TORC1/2 activation in driving mesangial cell hypertrophy.

Modulatory Role of Quercetin Against Gamma Radiation Mediated Biochemical and Morphological Alterations of Red Blood Cells

International Journal of Radiation Biology. Jan, 2013  |  Pubmed ID: 23363054

Abstract Purpose: The present work was intended to evaluate the radioprotective effect of quercetin against gamma radiation induced oxidative stress on Red Blood Cell (RBC). Materials and methods: Swiss albino male mice were treated with quercetin (100 mg/kg body wt.) for three consecutive days prior to 5 Gy (60)Co-gamma irradiation. RBC was isolated to estimate the level of intracellular reactive oxygen species (ROS), membrane lipid peroxidation (LPO), intracellular reduced glutathione (GSH), mean corpuscular hemoglobin concentration (MCHC), osmotic fragility and morphological alterations by atomic force microscope (AFM). Results: Irradiation increased intracellular ROS and membrane LPO whereas it decreased the intracellular GSH. Quercetin pretreatment ameliorated these alterations. The MCHC value decreased after irradiation whereas quercetin pretreatment restored it. The average osmotic fragility (H(50)) and the maximum rate of hemolysis (dH/dC)(max) increased after irradiation. Quercetin pretreatment decreased the H(50) and (dH/dC)(max). The AFM study showed that irradiation transformed RBC from biconcave to echinocytes, increased their surface roughness and decreased the vertical distance whereas pretreatment of quercetin significantly prevented both the alterations. Conclusions: Gamma radiation produced ROS and LPO which rendered oxidative stress and ultimately damaged RBC whereas, quercetin ameliorated these changes and protected RBC from radiation mediated damage.

CD271+ Bone Marrow Mesenchymal Stem Cells May Provide a Niche for Dormant Mycobacterium Tuberculosis

Science Translational Medicine. Jan, 2013  |  Pubmed ID: 23363977

Mycobacterium tuberculosis (Mtb) can persist in hostile intracellular microenvironments evading immune cells and drug treatment. However, the protective cellular niches where Mtb persists remain unclear. We report that Mtb may maintain long-term intracellular viability in a human bone marrow (BM)-derived CD271(+)/CD45(-) mesenchymal stem cell (BM-MSC) population in vitro. We also report that Mtb resides in an equivalent population of BM-MSCs in a mouse model of dormant tuberculosis infection. Viable Mtb was detected in CD271(+)/CD45(-) BM-MSCs isolated from individuals who had successfully completed months of anti-Mtb drug treatment. These results suggest that CD271(+) BM-MSCs may provide a long-term protective intracellular niche in the host in which dormant Mtb can reside.

1,3,5-Trisubstituted Benzenes As Fluorescent Photoaffinity Probes for Human Carbonic Anhydrase II Capture

Chemical Communications (Cambridge, England). Feb, 2013  |  Pubmed ID: 23364467

The synthesis of small molecule based 1,3,5-trisubstituted benzenes for photo-mediated capture of human carbonic anhydrase II with visualisation by fluorescence is described.

Assay Development for Identifying Inhibitors of the Mycobacterial FadD32 Activity

Journal of Biomolecular Screening. Jan, 2013  |  Pubmed ID: 23364516

FadD32, a fatty acyl-AMP ligase (FAAL32) involved in the biosynthesis of mycolic acids, major and specific lipid components of the mycobacterial cell envelope, is essential for the survival of Mycobacterium tuberculosis, the causative agent of tuberculosis. The protein catalyzes the conversion of fatty acid to acyl-adenylate (acyl-AMP) in the presence of adenosine triphosphate and is conserved in all the mycobacterial species sequenced so far, thus representing a promising target for the development of novel antituberculous drugs. Here, we describe the optimization of the protein purification procedure and the development of a high-throughput screening assay for FadD32 activity. This spectrophotometric assay measuring the release of inorganic phosphate was optimized using the Mycobacterium smegmatis FadD32 as a surrogate enzyme. We describe the use of T(m) (melting temperature) shift assay, which measures the modulation of FadD32 thermal stability, as a tool for the identification of potential ligands and for validation of compounds as inhibitors. Screening of a selected library of compounds led to the identification of five novel classes of inhibitors.

Pleural Fluid Cholesterol in Differentiating Exudative and Transudative Pleural Effusion

Pulmonary Medicine. 2013  |  Pubmed ID: 23365740

Objectives. To study the diagnostic value of pleural fluid cholesterol in differentiating transudative and exudative pleural effusion. To compare pleural fluid cholesterol level for exudates with Light's criteria. Design. Cross sectional descriptive study. Settings. Medical wards of Tribhuvan University Teaching Hospital. Methods. Sixty two cases of pleural effusion with definite clinical diagnosis admitted in TUTH were taken and classified as transudates (19) and exudates (43). The parameters pleural fluid protein/serum protein ratio (pfP/sP), pleural fluid LDH/ serum LDH ratio, pleural fluid LDH (pfLDH) and pleural fluid cholesterol (pCHOL) were compared with clinical diagnosis with regard to their usefulness for distinguishing between pleural exudates and transudates. Results. The pCHOL values determined were 1.92 ± 0.75 for exudates, 0.53 ± 0.28 for transudates, the differences between the transudates and others are statistically significant (P < 0.0001). It is seen that pfP/sP ratio has a sensitivity of 81.4% and specificity of 82.6%; pfLDH/sLDH ratio has a sensitivity of 86% and specificity of 94.7% and pCHOL with sensitivity of 97.7% and specificity of 100% for differentiating exudative and transudative PE. Conclusion. The determination of pCHOL is of great value for distinguishing between pleural exudates and transudates and should be included in routine laboratory analysis of pleural effusion.

Pathobiological Implications of MUC4 in Non-Small-Cell Lung Cancer

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer. Jan, 2013  |  Pubmed ID: 23370366

INTRODUCTION:: Altered expression of MUC4 plays an oncogenic role in various cancers, including pancreatic, ovarian, and breast. This study evaluates the expression and role of MUC4 in non-small-cell lung cancer (NSCLC). METHODS:: We used a paired system of MUC4-expressing (H292) and MUC4-nonexpressing (A549) NSCLC cell lines to analyze MUC4-dependent changes in growth rate, migration, and invasion using these sublines. We also evaluated the alterations of several tumor suppressor, proliferation, and metastasis markers with altered MUC4 expression. Furthermore, the association of MUC4 expression (by immunohistochemistry) in lung cancer samples with patient survival was evaluated. RESULTS:: MUC4-expressing lung cancer cells demonstrated a less proliferative and metastatic phenotype. Up-regulation of p53 in MUC4-expressing lung cancer cells led to the accumulation of cells at the G2/M phase of cell cycle progression. MUC4 expression attenuated Akt activation and decreased the expression of Cyclins D1 and E, but increased the expression of p21 and p27. MUC4 expression abrogated cancer cell migration and invasion by altering N- & E-cadherin expression and FAK phosphorylation. A decrease in MUC4 expression was observed with increasing tumor stage (mean composite score: stage I, 2.4; stage II, 1.8; stage III, 1.4; and metastatic, 1.2; p = 0.0093). Maximal MUC4 expression was associated with a better overall survival (p = 0.042). CONCLUSION:: MUC4 plays a tumor-suppressor role in NSCLC by altering p53 expression in NSCLC. Decrease in MUC4 expression in advanced tumor stages also seems to confirm the novel protective function of MUC4 in NSCLC.

Blood Stream Infection is Associated with Altered Heptavalent Pneumococcal Conjugate Vaccine Immune Responses in Very Low Birth Weight Infants

Journal of Perinatology : Official Journal of the California Perinatal Association. Jan, 2013  |  Pubmed ID: 23370608

OBJECTIVE:Sepsis in older children and adults modifies immune system function. We compared serotype-specific antibody responses to heptavalent pneumococcal conjugate vaccine (PCV7) in very low birth weight infants (<1500 g,VLBWs) with and without blood stream infection (BSI) during their birth hospitalization.STUDY DESIGN:Retrospective analysis of prospectively collected data for the Neonatal Research Network study of PCV7 responses among VLBWs. Infants received PCV7 at 2, 4 and 6 months after birth with blood drawn 4 to 6 weeks after third dose. Serotype antibodies were compared between infants with or without a history of BSI. Regression models were constructed with BW groups and other confounding factors identified in the primary study.RESULT:In all, 244 infants completed the vaccine series and had serum antibody available; 82 had BSI. After adjustment, BSI was not associated with reduced odds of serum antibody 0.35 μg ml(-1).CONCLUSION:BSI was not associated with reduced odds of World Health Organization-defined protective PCV7 responses in VLBWs.Journal of Perinatology advance online publication, 31 January 2013; doi:10.1038/jp.2013.5.

Diffusion-weighted Imaging of the Prostate: Comparison of B1000 and B2000 Image Sets for Index Lesion Detection

Journal of Magnetic Resonance Imaging : JMRI. Jan, 2013  |  Pubmed ID: 23371846

PURPOSE: To compare tumor detection on acquired diffusion-weighted (DW) images and apparent diffusion coefficient (ADC) maps, obtained using b-values of 1000 s/mm(2) and 2000 s/mm(2) , using radical prostatectomy as the reference. MATERIALS AND METHODS: In all, 29 prostate cancer patients who underwent 3T magnetic resonance imaging (MRI) including DW imaging using b-values of 1000 s/mm(2) and 2000 s/mm(2) were included. Two radiologists independently evaluated four image sets during different sessions and recorded the location and diameter of the dominant lesion: DW images acquired using b-values of 1000 s/mm(2) and 2000 s/mm(2) and ADC maps calculated using maximal b-values of 1000 s/mm(2) and 2000 s/mm(2) . Findings were correlated with the location and diameter of the dominant lesion at prostatectomy. Tumor-to-PZ contrast was also calculated, unblinded to pathology. RESULTS: Both readers achieved significantly higher sensitivity for DW images obtained using a b-value of 2000 s/mm(2) than 1000 s/mm(2) (P < 0.001), although there was no difference in sensitivity between ADC maps calculated using the two b-values (P ≥ 0.309). Tumor-to-PZ contrast was higher for DW images using a b-value of 2000 s/mm(2) (P = 0.067), although it was not different between the two corresponding ADC maps (P = 0.544). For both readers, correlations with tumor diameters were higher for either ADC map (r = 0.59-0.73) than for either acquired DW image set (r = 0.03-0.57). CONCLUSION: Use of a b-value of 2000 s/mm(2) compared with a b-value of 1000 s/mm(2) resulted in improved tumor sensitivity and higher tumor-to-PZ contrast on the acquired DW images, although performance of the ADC maps corresponding with the two b-values was similar. Correlation with tumor size was greater for either ADC map than for either acquired DW image set. J. Magn. Reson. Imaging 2013;. © 2013 Wiley Periodicals, Inc.

Potential Mechanisms of Action of Lithium in Bipolar Disorder : Current Understanding

CNS Drugs. Feb, 2013  |  Pubmed ID: 23371914

Lithium has been used for over half a century for the treatment of bipolar disorder as the archetypal mood stabilizer, and has a wealth of empirical evidence supporting its efficacy in this role. Despite this, the specific mechanisms by which lithium exerts its mood-stabilizing effects are not well understood. Given the inherently complex nature of the pathophysiology of bipolar disorder, this paper aims to capture what is known about the actions of lithium ranging from macroscopic changes in mood, cognition and brain structure, to its effects at the microscopic level on neurotransmission and intracellular and molecular pathways. A comprehensive literature search of databases including MEDLINE, EMBASE and PsycINFO was conducted using relevant keywords and the findings from the literature were then reviewed and synthesized. Numerous studies report that lithium is effective in the treatment of acute mania and for the long-term maintenance of mood and prophylaxis; in comparison, evidence for its efficacy in depression is modest. However, lithium possesses unique anti-suicidal properties that set it apart from other agents. With respect to cognition, studies suggest that lithium may reduce cognitive decline in patients; however, these findings require further investigation using both neuropsychological and functional neuroimaging probes. Interestingly, lithium appears to preserve or increase the volume of brain structures involved in emotional regulation such as the prefrontal cortex, hippocampus and amygdala, possibly reflecting its neuroprotective effects. At a neuronal level, lithium reduces excitatory (dopamine and glutamate) but increases inhibitory (GABA) neurotransmission; however, these broad effects are underpinned by complex neurotransmitter systems that strive to achieve homeostasis by way of compensatory changes. For example, at an intracellular and molecular level, lithium targets second-messenger systems that further modulate neurotransmission. For instance, the effects of lithium on the adenyl cyclase and phospho-inositide pathways, as well as protein kinase C, may serve to dampen excessive excitatory neurotransmission. In addition to these many putative mechanisms, it has also been proposed that the neuroprotective effects of lithium are key to its therapeutic actions. In this regard, lithium has been shown to reduce the oxidative stress that occurs with multiple episodes of mania and depression. Further, it increases protective proteins such as brain-derived neurotrophic factor and B-cell lymphoma 2, and reduces apoptotic processes through inhibition of glycogen synthase kinase 3 and autophagy. Overall, it is clear that the processes which underpin the therapeutic actions of lithium are sophisticated and most likely inter-related.

Hemorrhagic Gianotti-Crosti Syndrome in a One and Half Month Old Infant: An Extremely Unusual Presentation

Indian Journal of Dermatology. Jan, 2013  |  Pubmed ID: 23372217

Gianotti-Crosti syndrome is parainfectious exanthematous disease having unique presentation of small papulovesicular eruptions symmetrically over extensor surface of limbs and face in children. Hemorrhagic lesions are very rare and are always localized. Here, a case of EBV-induced Gianotti-Crosti syndrome with extensive hemorrhagic vesicles in a one and half month old infant, possibly induced by Epstein Barr virus, is reported. Neither the involvement of the disease at this early age nor the extensive hemorrhagic vesicles as the predominant presentation is reported before.

Hydrogen Bonding Interpolymer Complex Formation and Study of Its Host-Guest Interaction with Cyclodextrin and Its Application As an Active Delivery Vehicle

Langmuir : the ACS Journal of Surfaces and Colloids. Feb, 2013  |  Pubmed ID: 23373846

Interpolymer complex formation through hydrogen bonding has been investigated between two polymers: poly(acrylamide) (PAAm) and poly(vinyl alcohol) (PVA). The differential properties of the interpolymer complex with varying molecular weights of PVA have been studied by taking three different molecular weights of PVA. Furthermore, the host-guest interaction between the interpolymer complexes prepared and β-cyclodextrin (β-CD) has also been studied in detail. PAAm can form interpolymer complexes with PVA because of a cooperative hydrogen bonding interaction. The addition of β-CD to a dilute aqueous solution of PAAm-PVA results in a competition between interpolymer hydrogen bonding and host-guest interactions. In this article, we have tried to decipher the complex chemistry that occurs in the microheterogeneous solution. The PAAm-PVA binary system and the PAAm-PVA-β-CD ternary systems have been well characterized by using a fluorescent probe, coumarin-102. Dynamic light scattering (DLS), Fourier transform infrared (FTIR), fluorescence microscopy, and time-resolved fluorescence studies have been performed to substantiate steady-state fluorescence experiments. The results indicate the occurrence of a competitive interaction between the hydrogen bonding of the interpolymer complexes and the host-guest interaction with β-CD, whereby the later predominates. It is probable that the hydrophobic cavity of β-CD is threaded with linear polymers, thus forming a macromolecular supraassembly. It has also been concluded that PAAm preferentially interacts with β-CD by compromising its interaction with PVA. The enhanced deposition and retention of actives with this system was studied with a single species regrowth assay, antibacterial efficacy and the cell viability were studied using the live-dead staining protocol. This therefore opens new avenues in the targeted delivery of actives.

Pseudorapidity Density of Charged Particles in P+Pb Collisions at Sqrt[s_{NN}]=5.02  TeV

Physical Review Letters. Jan, 2013  |  Pubmed ID: 23373913

The charged-particle pseudorapidity density measured over four units of pseudorapidity in nonsingle-diffractive p+Pb collisions at a center-of-mass energy per nucleon pair sqrt[s_{NN}]=5.02  TeV is presented. The average value at midrapidity is measured to be 16.81±0.71  (syst), which corresponds to 2.14±0.17  (syst) per participating nucleon, calculated with the Glauber model. This is 16% lower than in nonsingle-diffractive pp collisions interpolated to the same collision energy and 84% higher than in d+Au collisions at sqrt[s_{NN}]=0.2  TeV. The measured pseudorapidity density in p+Pb collisions is compared to model predictions and provides new constraints on the description of particle production in high-energy nuclear collisions.

Conformational Coupling Across the Plasma Membrane in Activation of the EGF Receptor

Cell. Jan, 2013  |  Pubmed ID: 23374349

How the epidermal growth factor receptor (EGFR) activates is incompletely understood. The intracellular portion of the receptor is intrinsically active in solution, and to study its regulation, we measured autophosphorylation as a function of EGFR surface density in cells. Without EGF, intact EGFR escapes inhibition only at high surface densities. Although the transmembrane helix and the intracellular module together suffice for constitutive activity even at low densities, the intracellular module is inactivated when tethered on its own to the plasma membrane, and fluorescence cross-correlation shows that it fails to dimerize. NMR and functional data indicate that activation requires an N-terminal interaction between the transmembrane helices, which promotes an antiparallel interaction between juxtamembrane segments and release of inhibition by the membrane. We conclude that EGF binding removes steric constraints in the extracellular module, promoting activation through N-terminal association of the transmembrane helices.

Architecture and Membrane Interactions of the EGF Receptor

Cell. Jan, 2013  |  Pubmed ID: 23374350

Dimerization-driven activation of the intracellular kinase domains of the epidermal growth factor receptor (EGFR) upon extracellular ligand binding is crucial to cellular pathways regulating proliferation, migration, and differentiation. Inactive EGFR can exist as both monomers and dimers, suggesting that the mechanism regulating EGFR activity may be subtle. The membrane itself may play a role but creates substantial difficulties for structural studies. Our molecular dynamics simulations of membrane-embedded EGFR suggest that, in ligand-bound dimers, the extracellular domains assume conformations favoring dimerization of the transmembrane helices near their N termini, dimerization of the juxtamembrane segments, and formation of asymmetric (active) kinase dimers. In ligand-free dimers, by holding apart the N termini of the transmembrane helices, the extracellular domains instead favor C-terminal dimerization of the transmembrane helices, juxtamembrane segment dissociation and membrane burial, and formation of symmetric (inactive) kinase dimers. Electrostatic interactions of EGFR's intracellular module with the membrane are critical in maintaining this coupling.

Graphene Oxide in Cetyltrimethylammonium Bromide (CTAB) Reverse Micelle: A Befitting Soft Nanocomposite for Improving Efficiency of Surface-active Enzymes

Journal of Colloid and Interface Science. Jan, 2013  |  Pubmed ID: 23374433

Herein, we report the successful inclusion of 2D allotrope of carbon, graphene oxide (GO) in cetyltrimethylammonium bromide (CTAB)/isooctane/n-hexanol/water reverse micelle without compromising the stability of water-in-oil (w/o) microemulsion. This newly developed self-assembled nanocomposites act as proficient host for surface-active enzymes, lipase, horseradish peroxidase (HRP), and soybean peroxidase (SBP). Lipase activity within GO-doped CTAB reverse micelles remarkably improved by 3.8-fold compared to that was observed in only CTAB reverse micelle (second-order rate constant, k(2)=433±7cm(3)g(-1)s(-1)). In case of GO-doped CTAB reverse micelle, the observed enzyme activity (k(2)=1653±11cm(3)g(-1)s(-1)) is till date the highest ever activity of lipase in CTAB w/o microemulsions. In case of HRP and SBP, the catalytic efficiency maximally increased up to 2.6-fold and 2.3-fold, respectively. Electrostatic attraction between cationic head group of CTAB and anionic surface of GO as well as intrinsic amphiphilic character of GO possibly resulted in the confinement of this 2D nanosheet at the interface of reverse micelles. Integration of GO at the interface augmented the interfacial space in vicinity of surface-active enzyme. This enlarged interface might have accommodated higher amount of substrate and lipase with flexibility in its conformation resulting in marked improvement in the enzyme activity. Interfacial localization of GO was established by fluorescence spectroscopy. In addition, change in secondary structure of lipase in presence of 2D carbon allotrope was substantiated by circular dichroism spectroscopy.

Spatial and Temporal Variation and Hotspot Detection of Kala-azar Disease in Vaishali District (Bihar), India

BMC Infectious Diseases. Feb, 2013  |  Pubmed ID: 23375077

ABSTRACT: BACKGROUND: An improved understanding in transmission variation of kala-azar is fundamental to conduct surveillance and implementing disease prevention strategies. This study investigated the spatio-temporal patterns and hotspot detection for reporting kala-azar cases in Vaishali district based on spatial statistical analysis. METHODS: Epidemiological data from the study area during 2007--2011 was used to examine the dynamic space-time pattern of kala-azar outbreaks, and all cases were geocoded at a village level. Spatial smoothing was applied to reduce random noise in the data. Inverse distance weighting (IDW) is used to interpolate and predict the pattern of VL cases distribution across the district. Moran's I Index (Moran's I) statistics was used to evaluate autocorrelation in kala-azar spatial distribution and test how villages were clustered or dispersed in space. Getis-Ord Gi* (d) was used to identify the hotspot and cold spot areas within the study site. RESULTS: Mapping kala-azar cases or incidences reflects the spatial heterogeneity in the incidence rate of kala-azar affected villages in Vaishali district. Kala-azar incidence rate map showed most of the highest endemic villages were located in southern, eastern and northwestern part of the district; in the middle part of the district generally show the medium occurrence of VL. There was a significant positive spatial autocorrelation of kala-azar incidences for five consecutive years, with Moran's I statistic ranging from 0.04-0.17 (P <0.01). The results revealed spatially clustered patterns with significant differences by village. The hotspots showed the spatial trend of kala-azar diffusion (P < 0.01). CONCLUSIONS: The results pointed to the usefulness of spatial statistical approach to improve our understanding the spatio-temporal dynamics and control of kala-azar. The study also showed the north-western and southern part of Vaishali district is most likely endemic cluster region. To employ exact and geographically suitable risk-reduction programmes, apply of such spatial analysis tools should suit a vital constituent in epidemiology research and risk evaluation of kala-azar.

Factor Analysis Study on Sexual Responses in Women with Type 2 Diabetes Mellitus

Comprehensive Psychiatry. Jan, 2013  |  Pubmed ID: 23375262

AIMS: This study compared the components of sexual responses between Malaysian women with Type 2 diabetes mellitus and those without the disease. METHODS: This cross-sectional study measured sexual responses by using the validated Malay version of Female Sexual Function Index. A factor analysis with varimax rotation method was employed using principal component analysis to explore the correlation structure of the different domains of sexual responses between the two groups. Components of sexual responses were obtained using Kaiser's criteria and compared between those in the diabetic and non-diabetic groups. RESULTS: A total of 353 women (178 with diabetes and 175 without diabetes) were recruited. Three components of sexual responses emerged from the analysis in the study and control groups. Sexual pain was found to form a component together with lubrication and orgasm domains among the women with diabetes, unlike those without diabetes, where pain stood on its own. Sexual desire and arousal formed one component and satisfaction formed another in both groups. CONCLUSIONS: The domains in the sexual responses of Malaysian women were highly overlapping. It is concluded that the presence of pain as part of lubrication and orgasm component in women with diabetes indicates the importance of intact genital sensation, even though an adverse type of sensation, for vaginal congestion and orgasm to occur in this group of women.

β-Funaltrexamine Inhibits Chemokine (CXCL10) Expression in Normal Human Astrocytes

Neurochemistry International. Jan, 2013  |  Pubmed ID: 23376103

Neuroinflammation is an integral component of neurodegenerative disorders, CNS infection and trauma. Astroglial chemokines, such as CXCL10, are instrumental in neuroinflammatory signaling as well as neurotoxicity. We have utilized proinflammatory-induced CXCL10 expression in normal human astrocytes (NHA) as a model in which to assess the anti-inflammatory actions of the selective, mu-opioid receptor (MOR) antagonist, β-funaltrexamine (β-FNA). Interferon (IFN)γ+HIV-1 Tat-induced CXCL10 expression (secreted protein and mRNA) was inhibited by co-treatment with β-FNA. Neither the MOR-selective antagonist, D-Phe-Cys-Tyr-D-Trp-Arg-Pen-Thr-NH(2) (CTAP) nor the nonselective opioid receptor antagonist, naltrexone inhibited IFNγ+HIV-1 Tat-induced CXCL10 expression. Furthermore, co-treatment with excess CTAP or naltrexone did not prevent β-FNA mediated inhibition of IFNγ+HIV-1 Tat-induced CXCL10 expression. Additionally, we utilized an inhibitor of NF-κB activation (SN50) to demonstrate that IFNγ+HIV-1 Tat-induced CXCL10 expression is NF-κB-dependent in NHA. Subsequent experiments revealed that β-FNA did not significantly affect NF-κB activation. Interestingly, we discovered that β-FNA inhibited p38 activation as indicated by decreased expression of phospho-p38. Together, these findings suggest that the inhibitory actions of β-FNA are MOR-independent and mediated, in part, via a transcriptional mechanism. These findings add to our understanding of the mechanism by which chemokine expression is inhibited by β-FNA. In conjunction with future investigations, these novel findings are expected to provide insights into the development of safe and effective treatments for neuroinflammation.

Cross-protective Immunity Against Multiple Influenza Virus Subtypes by a Novel Modified Vaccinia Ankara (MVA) Vectored Vaccine in Mice

Vaccine. Jan, 2013  |  Pubmed ID: 23376279

Development of an influenza vaccine that provides cross-protective immunity remains a challenge. Candidate vaccines based on a recombinant modified vaccinia Ankara (MVA) viral vector expressing antigens from influenza (MVA/Flu) viruses were constructed. A vaccine candidate, designated MVA/HA(1)/C13L/NP, that expresses the hemagglutinin from pandemic H1N1 (A/California/04/09) and the nucleoprotein (N1) from highly pathogenic H5N1 (A/Vietnam/1203/04) fused to a secretory signal sequence from vaccinia virus was highly protective. The vaccine elicited strong antibody titers to homologous H1N1 viruses while cross-reactive antibodies to heterologous viruses were not detectable. In mice, this MVA/HA(1)/C13L/NP vaccine conferred complete protection against lethal challenge with A/Vietnam/1203/04 (H5N1), A/Norway/3487-2/09 (pandemic H1N1) or A/Influenza/Puerto Rico/8/34 (seasonal H1N1) and partial protection (57.1%) against challenge with seasonal H3N2 virus (A/Aichi/68). The protective efficacy of the vaccine was not affected by pre-existing immunity to vaccinia. Our findings highlight MVA as suitable vector to express multiple influenza antigens that could afford broad cross-protective immunity against multiple subtypes of influenza virus.

Proteome Changes Associated with Leishmania Donovani Promastigote Adaptation to Oxidative and Nitrosative Stress

Journal of Proteomics. Jan, 2013  |  Pubmed ID: 23376486

Phagocytic cells produce reactive oxygen and nitrogen species (ROS & RNS) as the most common arsenal to kill intracellular pathogens. Leishmania, an obligate intracellular pathogen also confronts this antimicrobial assault during the early phase of infection but nevertheless is able to survive these attacks and proliferate in macrophage. Adaptation of Leishmania to the toxic effects of ROS and RNS, involves a rapid change in the parasite proteome to combat the host defense response that macrophage mount in combating pathogen. To understand the events associated with combating ROS and RNS species, we performed a proteomic analysis of L. donovani promastigotes treated with sub-lethal doses of menadione (ROS), S-nitroso-N-acetylpenicillamine (RNS) or combination of both compounds. Proteomic changes triggered by these reagents were evaluated by iTRAQ labeling and subsequent LC-MALDI-TOF/TOF-MS analysis. Across the 3 stress conditions, the quantitative analysis identified changes in the proteins which encompass ~20% of the parasite proteome. Major changes were observed in enzymatic machinery of pathways involved in maintaining redox homeostasis, trypanothione metabolism, oxidative phosphorylation, superoxide metabolism, mitochondrial respiration process and other essential metabolic pathways. These observations shed light on how Leishmania promastigotes counter ROS and RNS affects during the initial stage of infection.

Decorating Single Layer Graphene Oxide with Electron Donor and Acceptor Molecules for the Study of Photoinduced Electron Transfer

Chemical Communications (Cambridge, England). Feb, 2013  |  Pubmed ID: 23380812

Graphene oxide decorated with an electron donor, zinc(ii) phthalocyanine, and an electron acceptor, fullerene, has been synthesized, and photoinduced electron transfer leading to charge-separation is reported.

Polariton Bose-Einstein Condensate at Room Temperature in an Al(Ga)N Nanowire-dielectric Microcavity with a Spatial Potential Trap

Proceedings of the National Academy of Sciences of the United States of America. Feb, 2013  |  Pubmed ID: 23382183

A spatial potential trap is formed in a 6.0-μm Al(Ga)N nanowire by varying the Al composition along its length during epitaxial growth. The polariton emission characteristics of a dielectric microcavity with the single nanowire embedded in-plane have been studied at room temperature. Excitation is provided at the Al(Ga)N end of the nanowire, and polariton emission is observed from the lowest bandgap GaN region within the potential trap. Comparison of the results with those measured in an identical microcavity with a uniform GaN nanowire and having an identical exciton-photon detuning suggests evaporative cooling of the polaritons as they are transported into the trap in the Al(Ga)N nanowire. Measurement of the spectral characteristics of the polariton emission, their momentum distribution, first-order spatial coherence, and time-resolved measurements of polariton cooling provides strong evidence of the formation of a near-equilibrium Bose-Einstein condensate in the GaN region of the nanowire at room temperature. In contrast, the condensate formed in the uniform GaN nanowire-dielectric microcavity without the spatial potential trap is only in self-equilibrium.

Tissue-Specific Upregulation of MDS/EVI Gene Transcripts in the Intestine by Thyroid Hormone During Xenopus Metamorphosis

PloS One. 2013  |  Pubmed ID: 23383234

Intestinal remodeling during amphibian metamorphosis resembles the maturation of the adult intestine during mammalian postembryonic development when the adult epithelial self-renewing system is established under the influence of high concentrations of plasma thyroid hormone (T3). This process involves de novo formation and subsequent proliferation and differentiation of the adult stem cells.

New HBV Subgenotype D9, a Novel D/C Recombinant, Identified in Patients with Chronic HBeAg-negative Infection in Eastern India

Journal of Viral Hepatitis. Mar, 2013  |  Pubmed ID: 23383660

Genome diversity is a hallmark of hepatitis B virus (HBV), which allowed its classification into 10 genotypes (A-J) and numerous subgenotypes. Among them, Genotype D is currently segregated into eight subgenotypes (D1-D8). Here, we report the identification and characterization of a novel subgenotype within genotype D of HBV from chronic hepatitis B e antigen (HBeAg)-negative patients of Eastern India. Phylogenetic tree analysis based on complete genome sequences revealed that six of 39 HBV/D isolates formed a distinct cluster supported by high bootstrap value and had nucleotide divergence >4% relative to the known D subgenotypes (D1-D8), justifying their assignment into a new subgenotype (D9). By comparing the amino acid sequences of the four ORFs of HBV/D9 with D1-D8, 36 specific residues, including a unique one (E(112) in the core region), were identified that could be considered as a signature of D9. Further analysis by Simplot, BootScan and jpHMM demonstrated that D9 resulted from a discrete recombination with genotype C over the precore-core region. This type of recombination has not been described previously as all C/D recombinants reported so far possessed genotype C backbones with mosaic fragments derived from HBV/D. Interestingly, compared to other subgenotypes of HBV/D, D9 isolates had a higher frequency of mutations (A1762T and G1764A) in the basal core promoter region that had been implicated in the development of hepatocellular carcinoma. Further investigations are needed to determine the overall prevalence and clinical significance of these newly characterized D9 strains and to assess the impact of inter-genotypic recombination on viral properties.

Measurement of the Semileptonic Charge Asymmetry Using B_{s}^{0}→D_{s}μX Decays

Physical Review Letters. Jan, 2013  |  Pubmed ID: 23383778

We present a measurement of the time-integrated flavor-specific semileptonic charge asymmetry in the decays of B_{s}^{0} mesons that have undergone flavor mixing, a_{sl}^{s}, using B_{s}^{0}(B[over ¯]_{s}^{0})→D_{s}^{∓}μ^{±}X decays, with D_{s}^{∓}→ϕπ^{∓} and ϕ→K^{+}K^{-}, using 10.4  fb^{-1} of proton-antiproton collisions collected by the D0 detector during Run II at the Fermilab Tevatron Collider. A fit to the difference between the time-integrated D_{s}^{-} and D_{s}^{+} mass distributions of the B_{s}^{0} and B[over ¯]_{s}^{0} candidates yields the flavor-specific asymmetry a_{sl}^{s}=[-1.12±0.74(stat)±0.17(syst)]%, which is the most precise measurement and in agreement with the standard model prediction.

Charge Separation Relative to the Reaction Plane in Pb-Pb Collisions at Sqrt[s_{NN}]=2.76  TeV

Physical Review Letters. Jan, 2013  |  Pubmed ID: 23383780

Measurements of charge-dependent azimuthal correlations with the ALICE detector at the LHC are reported for Pb-Pb collisions at sqrt[s_{NN}]=2.76  TeV. Two- and three-particle charge-dependent azimuthal correlations in the pseudorapidity range |η|<0.8 are presented as a function of the collision centrality, particle separation in pseudorapidity, and transverse momentum. A clear signal compatible with a charge-dependent separation relative to the reaction plane is observed, which shows little or no collision energy dependence when compared to measurements at RHIC energies. This provides a new insight for understanding the nature of the charge-dependent azimuthal correlations observed at RHIC and LHC energies.

Evidence for Associated Production of a Single Top Quark and W Boson in Pp Collisions at Sqrt[s]=7  TeV

Physical Review Letters. Jan, 2013  |  Pubmed ID: 23383893

Evidence is presented for the associated production of a single top quark and W boson in pp collisions at sqrt[s]=7  TeV with the CMS experiment at the LHC. The analyzed data correspond to an integrated luminosity of 4.9  fb^{-1}. The measurement is performed using events with two leptons and a jet originated from a b quark. A multivariate analysis based on kinematic properties is utilized to separate the tt[over ¯] background from the signal. The observed signal has a significance of 4.0σ and corresponds to a cross section of 16_{-4}^{+5}  pb, in agreement with the standard model expectation of 15.6±0.4_{-1.2}^{+1.0}  pb.

Nonstatistical Dynamic Effects in the Thermal C(2)-C(6) Diels-Alder Cyclization of Enyne-Allenes

The Journal of Organic Chemistry. Feb, 2013  |  Pubmed ID: 23384414

The Diels-Alder (DA) reaction channel of the thermal C(2)-C(6) (Schmittel) cyclization of enyne-allenes is studied computationally and experimentally evaluating the influence of temperature on product ratios. Remote substituents at the alkyne terminus influence the mechanism of the C(2)-C(6)/DA cyclization steering it either to a stepwise or a concerted course. Temperature independent product ratios, selectivity of product formation, and computational results obtained at (U)BLYP/6-31G(d) level unveil a mechanism that is strongly controlled by nonstatistical dynamics.

Genomics, Population Genetics and Evolutionary History of Plasmodium Vivax

Advances in Parasitology. 2013  |  Pubmed ID: 23384624

Plasmodium vivax is part of a highly diverse clade that includes several Plasmodium species found in nonhuman primates from Southeast Asia. The diversity of primate malarias in Asia is staggering; nevertheless, their origin was relatively recent in the evolution of Plasmodium. We discuss how humans acquired the lineage leading to P. vivax from a nonhuman primate determined by the complex geological processes that took place in Southeast Asia during the last few million years. We conclude that widespread population genomic investigations are needed in order to understand the demographic processes involved in the expansion of P. vivax in the human populations. India represents one of the few countries with widespread vivax malaria. Earlier studies have indicated high genetic polymorphism at antigenic loci and no evidence for geographic structuring. However, new studies using genetic markers in selectively neutral genetic regions indicate that Indian P. vivax presents complex evolutionary history but possesses features consistent with being part of the ancestral distribution range of this species. Such studies are possible due to the availability of the first P. vivax genome sequences. Next generation sequencing technologies are now paving the way for the sequencing of more P. vivax genomes that will dramatically increase our understanding of the unique biology of this species.

The Synthesis of Citrate-modified Silver Nanoparticles in an Aqueous Suspension of Graphene Oxide Nanosheets and Their Antibacterial Activity

Colloids and Surfaces. B, Biointerfaces. Jan, 2013  |  Pubmed ID: 23384688

A composite material consisting of silver nanoparticles (Ag NPs) deposited on graphene oxide (GO) nanosheets is prepared by chemical reduction of Ag metal ions by sodium borohydride (NaBH(4)) in the presence of trisodium citrate acting as a stabilizing agent to prevent agglomeration of the nanoparticles. The synthesized GO/Ag NPs composite was characterized by UV/vis spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and transmission electron microscopy (TEM). TEM analysis confirmed a high density of Ag NPs on the GO nanosheets with a particle size range of 2-25nm. The activity of the GO/Ag NPs suspension as an antibacterial agent against Gram positive bacteria Staphylococcus aureus and Bacillus subtilis was investigated. The percentage of the killing bacterial colonies by Ag NPs (without GO) is found to be 96-97% while 100% of killing bacterial colonies is only obtained using GO/Ag NPs suspension. Moreover, it was also observed that leakage of sugars and proteins from the cell wall of both S. aureus and B. subtilis in interaction with GO/Ag NPs suspension is higher compared to Ag NPs (without GO) and GO nanosheets.

Growth Kinetics and Immune Response of Chimeric Foot and Mouth Disease Virus Serotype 'O' Produced Through Replication Competent Mini Genome of Serotype Asia 1, 63/72, in BHK Cell Lines

Virus Research. Feb, 2013  |  Pubmed ID: 23384973

Regular vaccinations with potent vaccine, in endemic countries and vaccination to live in non-endemic countries are the methods available to control foot and mouth disease. Selection of candidate vaccine strain is not only cumbersome but the candidate should grow well for high potency vaccine preparation. Alternative strategy is to generate an infectious cDNA of a cell culture-adapted virus and use the replicon for development of tailor-made vaccines. We produced a chimeric 'O' virus in the backbone of Asia 1 and studied its characteristics. The chimeric virus showed high infectivity titre (>10(10)) in BHK21 cell lines, revealed small plaque morphology and there was no cross reactivity with antiserum against Asia1. The virus multiplies rapidly and reaches peak at 12h post infection. The vaccine prepared with this virus elicited high antibody titres.

Phosphodiesterase-5 Inhibitor, Tadalafil, Attenuates Oxidative Stress and Protects Against Myocardial Ischemia/reperfusion Injury in Type 2 Diabetic Mice

Free Radical Biology & Medicine. Feb, 2013  |  Pubmed ID: 23385031

Diabetic patient's exhibit increased risk for the development of cardiovascular diseases primarily due to impaired nitric oxide (NO) bioavailability. Phosphodiesterase-5 (PDE-5) inhibitor, sildenafil, restores NO signaling and protects against ischemia/reperfusion (I/R) injury. In this study, we determined the effect of long-acting PDE-5 inhibitor, tadalafil, on diabetes associated complications and its role in attenuating oxidative stress following I/R injury in type 2 diabetic db/db mice. Adult male db/db mice (n=40/group) were randomized to receive: DMSO (10%, 0.2ml, i.p.) or tadalafil (1mg/kg, i.p.) for 28 days. Following 28 days treatment, the hearts were isolated and subjected to 30min global ischemia followed by 60min reperfusion in Langendorff mode. Infarct size was measured using computer morphometry of tetrazolium stained sections. Cardiomyocytes were isolated from a subset of hearts and subjected to 40min simulated ischemia followed by 1h of reoxygenation (SI/RO). Dichlorodihydrofluorescein diacetate and JC-1 staining were used to measure ROS generation and mitochondrial membrane potential (Δψm), respectively. Another subset of hearts was used for the estimation of lipid peroxidation, glutathione and the expression of myocardial pRac1, Rac1, gp91phox, p47phox and p67phox by Western blot. Tadalafil treatment improved the metabolic status and reduced infarct size compared to the untreated db/db mice (21.2±1.8% vs 45.8±2.8%; p<0.01). The db/db mice showed enhanced oxidative stress in cardiomyocytes as indicated by significant increase in ROS production. Cardiac NAD(P)H oxidase activity, lipid peroxidation and oxidized glutathione were also increased in db/db mice as compared to non-diabetic control animals. Tadalafil treatment in db/db mice suppressed oxidative stress, attenuated myocardial expression of pRac1, gp91phox and also preserved the loss of Δψm in cardiomyocytes following SI/RO. In conclusion, these results demonstrate that chronic treatment with tadalafil attenuates oxidative stress and improves mitochondrial integrity while providing powerful cardioprotective effects in type 2 diabetes.

MRI Assessment of Uterine Artery Patency and Fibroid Infarction Rates 6 Months After Uterine Artery Embolization with Nonspherical Polyvinyl Alcohol

Cardiovascular and Interventional Radiology. Feb, 2013  |  Pubmed ID: 23385663

PURPOSE: We have observed significant rates of uterine artery patency after uterine artery embolization (UAE) with nonspherical polyvinyl alcohol (nsPVA) on 6 month follow-up MR scanning. The study aim was to quantitatively assess uterine artery patency after UAE with nsPVA and to assess the effect of continued uterine artery patency on outcomes. METHODS: A single centre, retrospective study of 50 patients undergoing bilateral UAE for uterine leiomyomata was undertaken. Pelvic MRI was performed before and 6 months after UAE. All embolizations were performed with nsPVA. Outcome measures included uterine artery patency, uterine and dominant fibroid volume, dominant fibroid percentage infarction, presence of ovarian arterial collaterals, and symptom scores assessed by the Uterine Fibroid Symptom and Quality of Life questionnaire (UFS-QOL). RESULTS: Magnetic resonance angiographic evidence of uterine artery recanalization was demonstrated in 90 % of the patients (64 % bilateral, 26 % unilateral) at 6 months. Eighty percent of all dominant fibroids demonstrated >90 % infarction. The mean percentage reduction in dominant fibroid volume was 35 %. No significant difference was identified between nonpatent, unilateral, and bilateral recanalization of the uterine arteries with regard to percentage dominant fibroid infarction or dominant fibroid volume reduction. The presence of bilaterally or unilaterally patent uterine arteries was not associated with inferior clinical outcomes (symptom score or UFS-QOL scores) at 6 months. CONCLUSION: The high rates of uterine artery patency challenge the current paradigm that nsPVA is a permanent embolic agent and that permanent uterine artery occlusion is necessary to optimally treat uterine fibroids. Despite high rates of uterine artery recanalization in this cohort, satisfactory fibroid infarction rates and UFS-QOL scores were achieved.

Congenital Portosystemic Venous Shunt in a Preterm Rh-Isoimmunized Infant

Indian Journal of Pediatrics. Feb, 2013  |  Pubmed ID: 23389350

The authors report a preterm infant with Rh-isoimmunization, who had persistent hepato-splenomegaly with conjugated hyperbilirubinemia, transaminitis, and hyperammonemia. Ultrasound abdomen revealed an intrahepatic portosystemic venous shunt (PSVS). The child was managed conservatively. On follow up at 2.4 y of age, the child is having normal growth and development, but with persisting shunt. Severe Rh-isoimmunisation in a neonate can sometimes share some of the features of congenital PSVS and delay the diagnosis of the latter. The index case had shunt ratio >80 % during the neonatal period but did not require any intervention.

Effect of Curcumin on the Diffusion Kinetics of a Hemicyanine Dye, LDS-698 Across a Lipid Bilayer Probed by Second Harmonic Spectroscopy

Langmuir : the ACS Journal of Surfaces and Colloids. Feb, 2013  |  Pubmed ID: 23391287

The diffusion kinetics of a hemicyanine dye, LDS-698, across model membrane bilayers was studied in real time by the surface specific second harmonic technique. Using liposomes made from different head groups it has been established that the diffusion is initiated by electrostatic adsorption of the positively charged dye to the outer surface of negatively charged liposomes and its time constant is affected by the rigidity of the bilayer. In the presence of the liphophilic drug Curcumin (Curcumin:lipid mole ratio ~0.2) the diffusion of LDS-698 was observed to be faster by ~56 times (from 780 to 14 second) at 250C. Under similar Curcumin concentration, when Cholesterol containing liposomes are used at 20C, the observed diffusion time constant increases from 14 to 65 second showing that the effect of Curcumin is superior to the effect of increasing bilayer rigidity on the diffusion process. Control experiments with other lipophilic molecules like DPH and Nile Red showed that the effect of liposomal Curcumin is superior. Consistent with previous reports of Curcumin affecting the bilayer organization, this study additionally demonstrates increased permeability of liposomal Curcumin, in particular against organic cations. It is speculated that origin of this enhanced membrane permeability by lipophilic molecules may depend upon the interaction of the molecule with the polar head group region of the lipid which, in turn, is expected to depend on the chemical structure of the molecule.

Using FDG-PET to Measure Early Treatment Response in Head and Neck Squamous Cell Carcinoma: Quantifying Intrinsic Variability in Order to Understand Treatment-Induced Change

AJNR. American Journal of Neuroradiology. Feb, 2013  |  Pubmed ID: 23391836

BACKGROUND AND PURPOSE:Quantification of both baseline variability and intratreatment change is necessary to optimally incorporate functional imaging into adaptive therapy strategies for HNSCC. Our aim was to define the baseline variability of SUV on FDG-PET scans in patients with head and neck squamous cell carcinoma and to compare it with early treatment-induced SUV change.MATERIALS AND METHODS:Patients with American Joint Committee on Cancer stages III-IV HNSCC were imaged with 2 baseline PET/CT scans and a third scan after 1-2 weeks of curative-intent chemoradiation. SUV(max) and SUV(mean) were measured in the primary tumor and most metabolically active nodal metastasis. Repeatability was assessed with Bland-Altman plots. Mean percentage differences (%ΔSUV) in baseline SUVs were compared with intratreatment %ΔSUV. The repeatability coefficient for baseline %ΔSUV was compared with intratreatment %ΔSUV.RESULTS:Seventeen patients had double-baseline imaging, and 15 of these patients also had intratreatment scans. Bland-Altman plots showed excellent baseline agreement for nodal metastases SUV(max) and SUV(mean), but not primary tumor SUVs. The mean baseline %ΔSUV was lowest for SUV(max) in nodes (7.6% ± 5.2%) and highest for SUV(max) in primary tumor (12.6% ± 9.2%). Corresponding mean intratreatment %ΔSUV(max) was 14.5% ± 21.6% for nodes and 15.2% ± 22.4% for primary tumor. The calculated RC for baseline nodal SUV(max) and SUV(mean) were 10% and 16%, respectively. The only patient with intratreatment %ΔSUV above these RCs was 1 of 2 patients with residual disease after CRT.CONCLUSIONS:Baseline SUV variability for HNSCC is less than intratreatment change for SUV in nodal disease. Evaluation of early treatment response should be measured quantitatively in nodal disease rather than the primary tumor, and assessment of response should consider intrinsic baseline variability.

A Highly Selective and Sensitive Probe for Colorimetric and Fluorogenic Detection of Cd(2+) in Aqueous Media

The Analyst. Feb, 2013  |  Pubmed ID: 23392200

A new rhodamine-quinoline based dyad has been synthesized. It shows a highly selective response to Cd(2+) in the presence of other competing metal ions in aqueous media (pH = 7.1). The detection limit of the sensor is in the 10(-7) M level.

Sequencing and Characterization of the Complete Mitochondrial Genomes of Three Pneumocystis Species Provide New Insights into Divergence Between Human and Rodent Pneumocystis

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology. Feb, 2013  |  Pubmed ID: 23392351

Pneumocystis jirovecii is an important opportunistic pathogen associated with AIDS and other immunodeficient conditions. Currently, very little is known about its nuclear and mitochondrial genomes. In this study, we sequenced the complete mitochondrial genome (mtDNA) of this organism and its closely related species Pneumocystis carinii and Pneumocystis murina by a combination of sequencing technologies. Our study shows that P. carinii and P. murina mtDNA share a nearly identical number and order of genes in a linear configuration, whereas P. jirovecii has a circular mtDNA containing nearly the same set of genes but in a different order. Detailed studies of the mtDNA terminal structures of P. murina and P. carinii suggest a unique replication mechanism for linear mtDNA. Phylogenetic analysis supports a close association of Pneumocystis species with Taphrina, Saitoella, and Schizosaccharomyces, and divergence within Pneumocystis species, with P. murina and P. carinii being more closely related to each other than either is to P. jirovecii. Comparative analysis of four complete P. jirovecii mtDNA sequences in this study and previously reported mtDNA sequences for diagnosing and genotyping suggests that the current diagnostic and typing methods can be improved using the complete mtDNA data. The availability of the complete P. jirovecii mtDNA also opens the possibility of identifying new therapeutic targets.-Ma, L., Huang, D. W., Cuomo, C. A., Sykes, S., Fantoni, G., Das, B., Sherman, B. T., Yang, J., Huber, C., Xia, Y., Davey, E., Kutty, G., Bishop, L., Sassi, M., Lempicki, R. A., Kovacs, J. A. Sequencing and characterization of the complete mitochondrial genomes of three Pneumocystis species provide new insights into divergence between human and rodent Pneumocystis.

An Effective and Secure Key-management Scheme for Hierarchical Access Control in E-medicine System

Journal of Medical Systems. Apr, 2013  |  Pubmed ID: 23392626

Recently several hierarchical access control schemes are proposed in the literature to provide security of e-medicine systems. However, most of them are either insecure against 'man-in-the-middle attack' or they require high storage and computational overheads. Wu and Chen proposed a key management method to solve dynamic access control problems in a user hierarchy based on hybrid cryptosystem. Though their scheme improves computational efficiency over Nikooghadam et al.'s approach, it suffers from large storage space for public parameters in public domain and computational inefficiency due to costly elliptic curve point multiplication. Recently, Nikooghadam and Zakerolhosseini showed that Wu-Chen's scheme is vulnerable to man-in-the-middle attack. In order to remedy this security weakness in Wu-Chen's scheme, they proposed a secure scheme which is again based on ECC (elliptic curve cryptography) and efficient one-way hash function. However, their scheme incurs huge computational cost for providing verification of public information in the public domain as their scheme uses ECC digital signature which is costly when compared to symmetric-key cryptosystem. In this paper, we propose an effective access control scheme in user hierarchy which is only based on symmetric-key cryptosystem and efficient one-way hash function. We show that our scheme reduces significantly the storage space for both public and private domains, and computational complexity when compared to Wu-Chen's scheme, Nikooghadam-Zakerolhosseini's scheme, and other related schemes. Through the informal and formal security analysis, we further show that our scheme is secure against different attacks and also man-in-the-middle attack. Moreover, dynamic access control problems in our scheme are also solved efficiently compared to other related schemes, making our scheme is much suitable for practical applications of e-medicine systems.

Temperature-Independent Catalytic Two-Electron Reduction of Dioxygen by Ferrocenes with a Copper(II) Tris[2-(2-pyridyl)ethyl]amine Catalyst in the Presence of Perchloric Acid

Journal of the American Chemical Society. Feb, 2013  |  Pubmed ID: 23394287

Selective two-electron plus two-proton (2e(-)/2H(+)) reduction of O(2) to hydrogen peroxide by ferrocene (Fc) or 1,1'-dimethylferrocene (Me(2)Fc) in the presence of perchloric acid is catalyzed efficiently by a mononuclear copper(II) complex, [Cu(II)(tepa)](2+) (1; tepa = tris[2-(2-pyridyl)ethyl]amine) in acetone. The E(1/2) value for [Cu(II)(tepa)](2+) as measured by cyclic voltammetry is 0.07 V vs Fc/Fc(+) in acetone, being significantly positive, which makes it possible to use relatively weak one-electron reductants such as Fc and Me(2)Fc for the overall two-electron reduction of O(2). Fast electron transfer from Fc or Me(2)Fc to 1 affords the corresponding Cu(I) complex [Cu(I)(tepa)](+) (2), which reacts at low temperature (193 K) with O(2), however only in the presence of HClO(4), to afford the hydroperoxo complex [Cu(II)(tepa)(OOH)](+) (3). A detailed kinetic study on the homogeneous catalytic system reveals the rate-determining step to be the O(2)-binding process in the presence of HClO(4) at lower temperature as well as at room temperature. The O(2)-binding kinetics in the presence of HClO(4) were studied, demonstrating that the rate of formation of the hydroperoxo complex 3 as well as the overall catalytic reaction remained virtually the same with changing temperature. The apparent lack of activation energy for the catalytic two-electron reduction of O(2) is shown to result from the existence of a pre-equilibrium between 2 and O(2) prior to the formation of the hydroperoxo complex 3. No further reduction of [Cu(II)(tepa)(OOH)](+) (3) by Fc or Me(2)Fc occurred, and instead 3 is protonated by HClO(4) to yield H(2)O(2) accompanied by regeneration of 1, thus completing the catalytic cycle for the two-electron reduction of O(2) by Fc or Me(2)Fc.

NAT2 Sequence Polymorphisms and Acetylation Profiles in Indians

Pharmacogenomics. Feb, 2013  |  Pubmed ID: 23394391

Background:NAT2, a broad-spectrum drug-metabolizing gene, is of high pharmacogenetic interest. Based on seven different mutations in the NAT2 gene, an individual can either be categorized as a slow or fast acetylator. Materials & methods: In order to characterize acetylation profiles of Indians, where data are poorly available, we sequenced the 873 bp NAT2 coding region in 250 Indians, covering the whole of India including three tribes. Results: Altogether, 35 NAT2 alleles forming two acetylator phenotypes (distributed almost in equal proportion in India) were found; while the alleles determining slow acetylators were highly differentiated, the fast acetylator alleles were less in number but highly frequent. Conclusion: Interestingly, distribution of two different acetylation phenotypes correlated well with historical dietary pattern in India. The neighbor-joining phylogenetic tree based on NAT2 gene polymorphisms in worldwide humans revealed genetic affinities among populations with similar acetylation phenotypes, which also placed Indians and Africans together in a single cluster. Original submitted 22 August 2012; Revision submitted 1 January 2013.

Additive Effect of Alpha-tocopherol and Ascorbic Acid in Combating Ethanol-induced Hepatic Fibrosis

Redox Report : Communications in Free Radical Research. 2013  |  Pubmed ID: 23394495

To investigate the efficacy of combined administration of alpha-tocopherol (AT) and ascorbic acid (AA) in reducing ethanol-induced hepatotoxicity.

Technique for Measuring Forward Light Scatter in Intraocular Lenses

Journal of Cataract and Refractive Surgery. Feb, 2013  |  Pubmed ID: 23395325

PURPOSE: To develop a technique for measuring the forward light scattering of intraocular lenses (IOLs). SETTING: The Scatter Works, Tucson, Arizona, USA. DESIGN: Evaluation of diagnostic technique. METHODS: A scatterometer with laser sources of 488 nm and 633 nm was used to directly measure the forward-scattered light of IOLs. These sources illuminated balanced salt solution-immersed IOLs within a cylindrical wet cell. The wet cell was placed at the center of rotation of a goniometer arm. On the end of the arm was a detector that measured the amount of laser light scattered from the IOL as a function of incident-beam angle. The measurements provided a profile of the scatter distribution for regions outside the directly transmitted beam. Forward and back light scatter was measured in new and artificially aged IOLs. RESULTS: Forward light scatter was increased in artificially aged IOLs compared with that in new unaged IOLs. The artificially aged IOLs developed sub-wavelength-diameter water nanoglistenings in the bulk material just below the surface. The measured scatter profiles were consistent with these subsurface droplets, suggesting Rayleigh-type scatter in the aged IOLs. The amount of light scatter from nanoglistenings does not appear to be sufficient to impair vision. Although the severely aged IOLs showed increased scatter, the level of increase was within 1 standard deviation of what is found in the normal population. CONCLUSION: A technique was developed enabling quantification of forward-scattered and back-scattered light from IOLs. FINANCIAL DISCLOSURE: Drs. Das and Karakelle are employees of Alcon Laboratories, Inc. Dr. Stover has received consultant fees and Dr. Schwiegerling research funding from Alcon Laboratories, Inc.

NANOG-dependent Function of TET1 and TET2 in Establishment of Pluripotency

Nature. Feb, 2013  |  Pubmed ID: 23395962

Molecular control of the pluripotent state is thought to reside in a core circuitry of master transcription factors including the homeodomain-containing protein NANOG, which has an essential role in establishing ground state pluripotency during somatic cell reprogramming. Whereas the genomic occupancy of NANOG has been extensively investigated, comparatively little is known about NANOG-associated proteins and their contribution to the NANOG-mediated reprogramming process. Using enhanced purification techniques and a stringent computational algorithm, we identify 27 high-confidence protein interaction partners of NANOG in mouse embryonic stem cells. These consist of 19 previously unknown partners of NANOG that have not been reported before, including the ten-eleven translocation (TET) family methylcytosine hydroxylase TET1. We confirm physical association of NANOG with TET1, and demonstrate that TET1, in synergy with NANOG, enhances the efficiency of reprogramming. We also find physical association and reprogramming synergy of TET2 with NANOG, and demonstrate that knockdown of TET2 abolishes the reprogramming synergy of NANOG with a catalytically deficient mutant of TET1. These results indicate that the physical interaction between NANOG and TET1/TET2 proteins facilitates reprogramming in a manner that is dependent on the catalytic activity of TET1/TET2. TET1 and NANOG co-occupy genomic loci of genes associated with both maintenance of pluripotency and lineage commitment in embryonic stem cells, and TET1 binding is reduced upon NANOG depletion. Co-expression of NANOG and TET1 increases 5-hydroxymethylcytosine levels at the top-ranked common target loci Esrrb and Oct4 (also called Pou5f1), resulting in priming of their expression before reprogramming to naive pluripotency. We propose that TET1 is recruited by NANOG to enhance the expression of a subset of key reprogramming target genes. These results provide an insight into the reprogramming mechanism of NANOG and uncover a new role for 5-methylcytosine hydroxylases in the establishment of naive pluripotency.

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