Bone Invasion in Oral Cancer Patients: a Comparison Between Orthopantamograph, Conventional Computed Tomography, and Single Positron Emission Computed Tomography

Journal of Cancer Research and Therapeutics. Oct-Dec, 2011  |  Pubmed ID: 22269406

One of the important factors in the pretreatment evaluation of patients with squamous cell carcinoma is the detection of the presence and extent of bone invasion by the tumor, which is significant for planning the therapy and determining the prognosis. Therefore, a study was undertaken with an objective to compare the accuracy and predictability of an Orthopantamograph (OPG), conventional Computed Tomography (CT), and Single Positron Emission Computed Tomography (SPECT) in the detection of bone invasion in squamous cell carcinoma patients scheduled to undergo surgery.

Emerging Role of Rasburicase in the Management of Increased Plasma Uric Acid Levels in Patients with Hematologic Malignancies

Journal of Blood Medicine. 2011  |  Pubmed ID: 22287858

Tumor lysis syndrome (TLS) is defined as a group of metabolic derangements that result from the massive and abrupt release of cellular components into the bloodstream after rapid lysis of tumor cells. Breakdown of released materials leads to a number of electrolyte abnormalities, including elevated uric acid concentrations in the blood (hyperuricemia), which carries potentially serious consequences. The diagnosis, prevention, and management of TLS is complicated by variability in definitions, differences in risk factors based on patient- and tumor-specific characteristics, and practitioner preferences in terms of pharmaceutical management strategies. The best prevention and management option for a particular patient depends on the patient's baseline risk for TLS development, the severity of symptoms in the event of TLS development, practical management considerations, and financial implications of treatment.

Salvage Use of Activated Recombinant Factor VII in the Management of Refractory Bleeding Following Cardiac Surgery

Journal of Blood Medicine. 2011  |  Pubmed ID: 22287872

Refractory post cardiopulmonary bypass (CPB) bleeding continues to cause concern for cardiac surgeons and intensivists. Massive postoperative hemorrhage following CPB is multifactorial and not fully understood, and it is also associated with increased mortality and morbidity. Activated recombinant factor VII (rFVIIa) has emerged as possible salvage medication in refractory post cardiac surgical bleeding. This observational study sought to identify the pattern of use of rFVIIa in cardiac surgery, its effectiveness, and risk.

Sleep Disturbances in Pediatric Depression

Asian Journal of Psychiatry. Dec, 2011  |  Pubmed ID: 22287998

Depressive illness beginning early in life can have serious developmental and functional consequences. Therefore, understanding its etiology and pathophysiology during this developmental stage is critical for developing effective prevention and intervention strategies. There is considerable evidence of sleep alterations in adult major depressive disorder. However, studies in children and adolescents have not found consistent changes in sleep architecture paralleling adult depression. This review article summarizes sleep polysomnography research in early-onset depression, highlighting the factors associated with variable findings across studies. In addition, potential avenues for future research will be suggested in order to develop more comprehensive theoretical models and interventions for pediatric depression.

Extensively Drug-resistant Tuberculosis: Experience at the Tuberculosis Research Centre, Chennai, India

The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease. Oct, 2011  |  Pubmed ID: 22283888

Ten extensively drug-resistant tuberculosis (XDR-TB) patients were identi ed among 104 human immunode ciency virus negative multidrug-resistant tuberculosis (MDR-TB) patients treated at the Tuberculosis Research Centre, Chennai, India, in two different cohorts between 1999-2003 and 2006-2007. They were managed with individualised treatment regimens. At the time of diagnosis of MDR-TB, one patient had XDR-TB and three had initial o oxacin resistance. One patient who had had a lobectomy in addition to chemotherapy became bacteriologically negative, three died, three defaulted and the remaining three, who are bacteriologically positive, are still continuing treatment. Although based on a small number of patients, our results have not been encouraging.

Lesson of the Month (2). An Unique Presentation of Infective Endocarditis

Clinical Medicine (London, England). Dec, 2011  |  Pubmed ID: 22268325

This lesson reports the case of endophthalmitis, a rare presentation of infective endocarditis (IE), two months following cardiac surgery. Although inflammatory markers were increased, blood cultures were negative. Transoesophageal echocardiography demonstrated an aortic root abscess. Culture of tissue obtained at surgery revealed the infective organism to be Aspergillus fumigatus, a rare cause of IE in the immunocompetent patient.

Codon 72 and G13964C Intron 6 Polymorphisms of TP53 in Relation to Development and Progression of Breast Cancer in India

Asian Pacific Journal of Cancer Prevention : APJCP. 2011  |  Pubmed ID: 22292621

The p53 protein is at the center of cell regulatory pathways influencing transcription and activity of several replication and transcription factors. In exon 4 of the gene TP53, a codon 72 polymorphism causing an Arg/Pro substitution has been reported in breast and other cancers. This substitution is in the putative SH3 binding domain of p53 protein, influencing binding capacity and thereby functional properties. In the present investigation of a relatively large series of cases in India, the frequency of the homozygous arginine genotype (33.2%) was significantly higher in the breast cancer group as compared to controls (19.6%), χ2 =11.791 (P=0.003). Patients with premenopausal breast cancer had a more elevated frequency (41.1%) than postmenopausal cases (25.4%) although the genotype frequency distribution did not show significant variation with respect to hormonal receptor status. Elevation was greatest in patients in advanced stages of cancer. The hetrozygote frequency (Arg/Pro) was also found to be increased in overweight and obese women with breast cancer. TP53 codon 72 polymorphism might predispose individual for the development of breast cancer as well as to bad prognosis. Intronic variants may affect gene regulation through aberrant splicing or through disruption of critical DNA - protein interaction. While no significant association was observed with relation to CC genotype as well as C allele of G13964C intron polymorphism with breast cancer, the C allele frequency showed association with respect to other risk confounding factors which might play role in progression of breast cancer.

Community-based Mental Health Intervention for Underprivileged Women in Rural India: an Experiential Report

International Journal of Family Medicine. 2011  |  Pubmed ID: 22295190

Objective. To share experiences from a project that integrates a mental health intervention within a developmental framework of microcredit activity for economically underprivileged women in rural India. Method. The mental health intervention had two components: group counseling and stress management. The former comprised of ventilation and reassurance and the latter strengthening of coping skills and a relaxation technique. Focus group discussions were used to understand women's perception of how microcredit economic activity and the mental health intervention had affected their lives. Results. Women in the mental health intervention group reported reduction in psychological distress and bodily aches and pains. Majority (86%) reported that the quality of their sleep had improved with regular practice of relaxation and that sharing their problems in the group had helped them to unburden. The social support extended by the members to each other, made them feel that they were not alone and could face any life situation. Conclusion. The study provided qualitative evidence that adding the mental health intervention to the ongoing economic activity had made a positive difference in the lives of the women. Addressing mental health concerns along with livelihood initiatives can help to enhance both economic and social capital in rural poor women.

A Comparative Analysis of Biomarker Expression and Molecular Subtypes of Pure Ductal Carcinoma In Situ and Invasive Breast Carcinoma by Image Analysis: Relationship of the Subtypes with Histologic Grade, Ki67, P53 Overexpression, and DNA Ploidy

International Journal of Breast Cancer. 2011  |  Pubmed ID: 22295212

There is a paucity of data regarding molecular subtypes of pure ductal carcinoma in situ (pDCIS). We evaluated the expression of ER, PR, HER2, Ki67, and p53 and DNA ploidy in 118 pDCIS and 100 invasive breast carcinomas (IBCAs) by routine IHC and classified them according to molecular subtypes. Quantification of biomarkers and DNA ploidy was performed by image analysis. Expression of ER, PR, and high ki67 was more frequent in pDCIS compared to IBCA. High-grade tumors had lower ER and PR expression, high Ki67, overexpression of HER2 and p53, and DNA aneuploidy. Luminal A and HER2 subtypes were more common in pDCIS, and triple negative was more prevalent in IBCA. In both groups, HER2 and triple negative subtypes were characterized by high ki67, overexpression of p53, and DNA aneuploidy compared to luminal subtypes. Molecular subtypes of IBCA are distinct from those of pDCIS. Invasion is characterized by change in phenotype in some tumors.

A Case of Successful Treatment of Comorbid Obesity and Polycystic Ovarian Disease with Add-on Metformin in Bipolar Disorder

The Primary Care Companion to CNS Disorders. 2011  |  Pubmed ID: 22295263

[The Study of Several Aldehyde Molecules by Raman Spectroscopy]

Guang Pu Xue Yu Guang Pu Fen Xi = Guang Pu. Dec, 2011  |  Pubmed ID: 22295776

The Raman spectra of formaldehyde, acetaldehyde, propionaldehyde and n-butyraladehyde (CnH2nO,n = 1, 2, 3, 4) were obtained by portable Raman spectrometer. The molecules of the four aldehydes were calculated by density functional theory (DFT). By comparing the calculated result and the experimental result, the bands of these Raman spectra were assigned. And the Raman spectra of these aldehydes molecules were analyzed and compared. These aldehydes could be real-time rapidly identified by Raman spectroscopy technology.

Piper Betel Linn (betel Vine), the Maligned Southeast Asian Medicinal Plant Possesses Cancer Preventive Effects: Time to Reconsider the Wronged Opinion

Asian Pacific Journal of Cancer Prevention : APJCP. 2011  |  Pubmed ID: 22296348

Since antiquity, Piper betel Linn (betel vine; family Piperaceae) has been an important medicinal agent in the various traditional and folk systems of medicine in Southeast Asia countries. The leaves are the most valued plant part and in the past were routinely used as a chewing agent to prevent halitosis. The leaves are also supposed to harden the gum, conserve the teeth and to prevent indigestion, bronchitis, constipation, congestion, coughs and asthma. Innumerable scientific studies have validated the ethnomedicinal claims. Betel leaves are an integral component of the betel quid that consists of areca nut (Areca catechu Linn.), tobacco (Nicotiana tabacum L) and slaked lime; a highly abused agent with carcinogenic properties. Regular chewing of betel quid is associated mainly with oral cancer and detail studies with individual constituents of the quid have shown that both tobacco and areca nut are carcinogenic, while slaked lime is shown to promote the process of carcinogenesis. However unlike other constituents of the betel quid, the betel leaves devoid carcinogenic effects and on the contrary possesses cancer preventive effects including against the carcinogens present in tobacco. This review for the first time provides information on cancer preventive effects and also addresses the various mechanisms which might be involved.

Characteristics of Aedes (stegomyia) Albopictus Skuse (diptera:culicidae) Breeding Sites

The Southeast Asian Journal of Tropical Medicine and Public Health. Sep, 2011  |  Pubmed ID: 22299432

We investigated the physicochemical characteristics of Aedes albopictus Skuse viz. breeding sites, by examining coconut shells, tires and plastic containers in a chikungunya affected area of Calicut, India. The study design was a cross-sectional ecological type. Thirty-four water samples were collected randomly from coconut shells, tires and plastic containers. The larvae were counted and the water was examined. The mean number of larvae per 500 ml was significantly higher in coconut shells than in tires and plastic containers. A negative correlation was observed with pH and a positive correlation was seen with most other variables. Coconut shells were the preferred breeding site for Ae. albopictus mosquitoes in our study. The rich organic content, low illumination and small orifice of the coconut shells could be the reasons for this. The higher salinity of the coconut shells did not affect breeding or survival.

Effect of Marriage on Pre-existing Psychoses

Indian Journal of Psychiatry. Oct, 2011  |  Pubmed ID: 22303035

Proton Magnetic Resonance Spectroscopy in Depression

Indian Journal of Psychiatry. Oct, 2011  |  Pubmed ID: 22303038

Magnetic Resonance Spectroscopy (MRS) is a unique technique that can directly assess the concentration of various biochemical metabolites in the brain. Thus, it is used in the study of molecular pathophysiology of different neuropsychiatric disorders, such as, the major depressive disorder and has been an area of active research. We conducted a computer-based literature search using the Pubmed database with 'magnetic resonance spectroscopy', 'MRS', 'depression', and 'major depressive disorder' as the key words, supplemented by a manual search of bibliographic cross-referencing. Studies in depression report abnormalities in the frontal cortex, basal ganglia, hippocampus, anterior cingulate cortex, and the occipital cortex. These abnormalities improve after treatment with selective serotonin reuptake inhibitor, electroconvulsive therapy, and yoga, and thus, are possibly state-dependent. The findings are consistent with other morphometric and clinical studies and support the proposed pathophysiological theory of dysfunction in the neuronal circuits involving the frontal cortex, limbic cortex, and basal ganglia. Spectroscopy also has potential implications in predicting the response to treatment and formulating individualized pharmacotherapy.

In Vitro Dissolution Studies on Solid Dispersions of Mefenamic Acid

Indian Journal of Pharmaceutical Sciences. Mar, 2011  |  Pubmed ID: 22303074

Solid dispersions of mefanamic acid with a water-soluble polymer polyvinyl pyrrolidine and a super disintegrant, primojel were prepared by common solvent and solvent evaporation methods employing methanol as the solvent. The dissolution rate and dissolution efficiency of the prepared solid dispersions were evaluated in comparison to the corresponding pure drug. Solid dispersions of mefenamic acid showed a marked enhancement in dissolution rate and dissolution efficiency. At 1:4 ratio of mefenamic acid-primojel a 2.61 fold increase in the dissolution rate of mefenamic acid was observed with solid dispersion. The solid dispersions in combined carriers gave much higher rates of dissolution than super disintegrants alone. Mefanamic acid-primojel-polyvinyl pyrrolidine (1:3.2:0.8) solid dispersion gave a 4.11 fold increase in the dissolution rate of mefenamic acid. Super disintegrants alone or in combination with polyvinyl pyrrolidine could be used to enhance the dissolution rate of mefenamic acid.

An Unusual Case of Altered Mental Status in a Young Woman

North American Journal of Medical Sciences. Nov, 2011  |  Pubmed ID: 22361499

We describe a case of paraneoplastic neurologic syndrome, namely N-Methyl-D-Aspartic acid receptor antibody associated limbic encephalitis, a rare cause of altered mental status in the young.

Silver Triflate Catalyzed Synthesis of 3-aminoalkylated Indoles and Evaluation of Their Antibacterial Activities

Organic and Medicinal Chemistry Letters. 2011  |  Pubmed ID: 22373086

ABSTRACT: An efficient, one-pot synthesis was developed for 3-aminoalkylated indoles by three-component coupling reaction of aldehydes, N-methylanilines, and indoles using AgOTf as a catalyst. A series of twenty 3-aminoalkylated indoles was evaluated for their antibacterial activities against both Gram negative and Gram positive bacteria. Compounds 4b and 4r showed good antibacterial activity against both Gram positive and Gram negative strains. However, inversing the property of substituent (from 4r to 4q) resulted in the significant fall in the magnitude of antibacterial activity against Escherichia coli.

Influence of Cell Specific Productivity on Product Quality

BMC Proceedings. Nov, 2011  |  Pubmed ID: 22373186

Enriching Rare Variants Using Family-specific Linkage Information

BMC Proceedings. Nov, 2011  |  Pubmed ID: 22373363

Genome-wide association studies have been successful in identifying common variants for common complex traits in recent years. However, common variants have generally failed to explain substantial proportions of the trait heritabilities. Rare variants, structural variations, and gene-gene and gene-environment interactions, among others, have been suggested as potential sources of the so-called missing heritability. With the advent of exome-wide and whole-genome next-generation sequencing technologies, finding rare variants in functionally important sites (e.g., protein-coding regions) becomes feasible. We investigate the role of linkage information to select families enriched for rare variants using the simulated Genetic Analysis Workshop 17 data. In each replicate of simulated phenotypes Q1 and Q2 on 697 subjects in 8 extended pedigrees, we select one pedigree with the largest family-specific LOD score. Across all 200 replications, we compare the probability that rare causal alleles will be carried in the selected pedigree versus a randomly chosen pedigree. One example of successful enrichment was exhibited for gene VEGFC. The causal variant had minor allele frequency of 0.0717% in the simulated unrelated individuals and explained about 0.1% of the phenotypic variance. However, it explained 7.9% of the phenotypic variance in the eight simulated pedigrees and 23.8% in the family that carried the minor allele. The carrier's family was selected in all 200 replications. Thus our results show that family-specific linkage information is useful for selecting families for sequencing, thus ensuring that rare functional variants are segregating in the sequencing samples.

Application of Collapsing Methods for Continuous Traits to the Genetic Analysis Workshop 17 Exome Sequence Data

BMC Proceedings. Nov, 2011  |  Pubmed ID: 22373425

Genetic Analysis Workshop 17 used real sequence data from the 1000 Genomes Project and simulated phenotypes influenced by a large number of rare variants. Our aim is to evaluate the performance of various collapsing methods that were developed for analysis of multiple rare variants. We apply collapsing methods to continuous phenotypes Q1 and Q2 for all 200 replicates of the unrelated individuals data. Within each gene, we collapse (1) all SNPs, (2) all SNPs with minor allele frequency (MAF) < 0.05, and (3) nonsynonymous SNPs with MAF < 0.05. We consider two tests when collapsing variants: using the proportion of variants and using the presence/absence of any variant. We also compare our results to a single-marker analysis using PLINK. For phenotype Q1, the proportion test for collapsing rare nonsynonymous SNPs often performed the best. Two genes (FLT1 and KDR) had statistically significant results. A single-marker analysis using PLINK also provided statistically significant results for some SNPs within these two genes. For phenotype Q2, collapsing rare nonsynonymous SNPs performed the best, with almost no difference between proportion and presence tests. However, neither collapsing methods nor a single-marker analysis provided statistically significant results at the true genes for Q2. We also found that a large number of noncausal genes had high correlations with causal genes for Q1 and Q2, which may account for inflated false positives.

From the Editor's Desk

Journal of Human Reproductive Sciences. Sep, 2011  |  Pubmed ID: 22346075

Parameter Optimization of Unbaffled Circular Surface Aeration Tank

Journal of Environmental Science & Engineering. Jan, 2011  |  Pubmed ID: 22324141

The efficiency of the surface aeration systems is generally governed by the geometric and dynamic parameters. The geometry is important because successful translation of the laboratory finding can be scaled up to field installations. Experimental optimization of the geometrical parameters (classical approach of one parameter variations at a time) has certain limitations, because it assumes a linear relationship among the various geometric parameters. In the real experimental process, it is not possible to vary all the parameters simultaneously. In such a case, the model of the system is built through computer simulation, assuming that the model will result in adequate determination of the optimum conditions for the real system. In this paper, two approaches have been used to model the phenomena in unbaffled circular surface aerators: i) Multiple regression and ii) Neural network. It has been found that neural network approach is showing better predictability compared to the multiple regression approach. In process of optimization, the pertinent dynamic parameter is divided into a finite number of segments over the entire range of observations. For each segment of the dynamic parameter, the neural network model is optimized for the geometrical parameters spanning over the entire range of observations. Thus each segment of the dynamic parameter has its set of optimal geometrical conditions. Results obtained are having less variation among them and they are very nearer to the experimental optimal conditions. Input parameter significance test of neural network model reveals that blade width of the rotor is the most significant geometric parameter for the aeration process.

Celiac Disease Preceding Crohn's Disease?

Tropical Gastroenterology : Official Journal of the Digestive Diseases Foundation. Jul-Sep, 2011  |  Pubmed ID: 22332346

A Review on the Therapeutic Potential of Embryonic and Induced Pluripotent Stem Cells in Hepatic Repair

Journal of Natural Science, Biology, and Medicine. Jul, 2011  |  Pubmed ID: 22346225

Despite the liver being proliferatively quiescent, it maintains balance between cell gain and cell loss, invokes a rapid regenerative response following hepatocyte loss, and restores liver mass. Human liver has immense regenerative capacity. Liver comprises many cell types with specialized functions. Of these cell types, hepatocytes play several key roles, but are most vulnerable to damage. Recent studies suggest that the extrahepatic stem cell pool contributes to liver regeneration. Stem cell therapies have the potential to enhance hepatic regeneration. Both embryonic and induced pluripotent stem cells could be a suitable source to regenerate hepatocytes. In the present review, we discuss the therapeutic potential of stem cells in hepatic repair and focus on the clinical applications of stem cells.

Wish You Were Here!

PDA Journal of Pharmaceutical Science and Technology / PDA. May, 2011  |  Pubmed ID: 22293230

Welcome to the IPDA!

PDA Journal of Pharmaceutical Science and Technology / PDA. Sep, 2011  |  Pubmed ID: 22293832

Acyclovir in Bipolar Disorder: a Mismatched Combination?

Indian Journal of Psychological Medicine. Jul, 2011  |  Pubmed ID: 22345854

Acyclovir, a commonly used antiviral drug can rarely result in neuropsychiatric complications especially in elderly. We for the first time report acyclovir associated hypomania in an elderly woman. Our report suggests that acyclovir is a risk factor for mood episode in vulnerable individual and one need to be cautious while using antiviral agents in patients with psychiatric disorders.

Association of CYP3A5*3 Polymorphism with Development of Acute Leukemia

Indian Journal of Human Genetics. Sep, 2011  |  Pubmed ID: 22345989

CYP3A5 was observed to be an important genetic contributor to inter individual differences in CYP3A-dependent drug metabolism in acute leukemic patients. Loss of CYP3A5 expression was mainly conferred by a single nucleotide polymorphism at 6986A>G (CYP3A5*3). We investigated the association between CYP3A5*3 polymorphism and acute leukemia.

Mortality in Mechanically Ventilated Patients of Guillain Barré Syndrome

Annals of Indian Academy of Neurology. Oct, 2011  |  Pubmed ID: 22346014

The mortality of patients with Guillain Barré syndrome (GBS) has varied widely with rates between 1-18%. Death results from pneumonia, sepsis, adult respiratory distress syndrome (ARDS) and less frequently due to autonomic dysfunction or pulmonary embolism. There are only few studies which have used a large sample and have in detail analyzed the circumstances relating to death and the prognostic factors for the same in a cohort, including only mechanically ventilated patients.

Work-related Musculoskeletal Disorders Among Dental Surgeons: A Pilot Study

Contemporary Clinical Dentistry. Oct, 2011  |  Pubmed ID: 22346158

To describe the work-related musculoskeletal disorders among on-job dental surgeons.

Non Syndromic Unilateral Dentigerous Cyst in a 4-year-old Child: A Rare Case Report

Contemporary Clinical Dentistry. Oct, 2011  |  Pubmed ID: 22346177

Dentigerous cyst is the most prevalent type of odontogenic cyst and is associated with crown of an unerupted or a developing tooth and accounts more than 24% of jaw cysts. Here, we present an interesting case of dentigerous cyst in a 4-year-old boy, which developed around an unerupted maxillary first premolar. Histological examination revealed a cyst with 1-2-cell-thick epithelial lining and presence of inflammatory cells in the connective tissue.

Prevalence and Determinants of Obesity in the Adult Population of Kanpur District -- a Population-based Study

Journal of the Indian Medical Association. Aug, 2011  |  Pubmed ID: 22315858

Worldwide, obesity is the most prevalent form of malnutrition. It is one of the most significant contributors to ill health and an indirect cause of morbidity and mortality resulting from hyperlipidaemia and glucose intolerance. Very few studies on the prevalence of obesity have been reported from developing countries like India. The present study was therefore undertaken to determine the prevalence of obesity and its predictors in the Indian community. The objectives are: (1) To determine the prevalence of obesity, (2) to study the relationship of obesity with age, (3) to identify the predictors of obesity. This community-based cross-sectional study was conducted on 801 subjects, aged 20 years and above in Kanpur District, using multistage stratified random sampling technique. Data was analysed using the software statistical package for social sciences 10.0.1 for windows. Prevalence of obesity was found to be 4.7%. An increase in body mass index was seen with increasing age. A higher prevalence of obesity was seen in the urban population and in women. Age, gender and daily intake of saturated fatty acids were found to be the main predictors of the obesity. An increase in the level of physical activity resulted in a decrease in the prevalence of obesity (odd's ratio = 0.36). Obesity is an emerging public health problem in the Indian population which indicates that intervention at the primary healthcare level, especially in diet and activity, are important for its prevention.

Maintaining Reduced Noise Levels in a Resource Constrained Neonatal Intensive Care Unit by Operant Conditioning

Indian Pediatrics. Jan, 2012  |  Pubmed ID: 22317987

OBJECTIVE: To evaluate the efficacy of operant conditioning in sustaining reduced noise levels in the neonatal intensive care unit (NICU) DESIGN: Quasi-experimental study on quality of care. SETTING: Level III NICU of a teaching hospital in south India. PARTICIPANTS: 26 staff employed in the NICU. (7 Doctors, 13 Nursing staff and 6 Nursing assistants). INTERVENTION: Operant conditioning of staff activity for 6 months. This method involves positive and negative reinforcement to condition the staff to modify noise generating activities. MAIN OUTCOME MEASURES: Comparing noise levels in decibel: A weighted [dB (A)] before conditioning with levels at 18 and 24 months after conditioning. Decibel: A weighted accounts for noise that is audible to human ears. RESULTS: Operant conditioning for 6 months sustains the reduced noise levels to within 62 dB (A) in ventilator room (95% CI: 60.4-62.2) and isolation room (95% CI: 55.8 -61.5). In the pre-term room, noise can be maintained within 52 dB (A) (95% CI: 50.8 -52.6). This effect is statistically significant in all the rooms at 18 months (P = 0.001). At 24 months post conditioning there is a significant rebound of noise levels by 8.6, 6.7 and 9.9 dB (A) in the ventilator, isolation and pre-term room, respectively (P=0.001). CONCLUSION: Operant conditioning for 6 months was effective in sustaining reduced noise levels. At 18 months post conditioning, the noise levels were maintained within 62 dB (A), 60 dB (A) and 52 dB (A) in the ventilator, isolation and pre-term room, respectively. Conditioning needs to be repeated at 12 months in the ventilator room and at 18 months in the other rooms.

Cirsoid Aneurysm of Scalp

Journal of Neurosciences in Rural Practice. Jan, 2012  |  Pubmed ID: 22346211

Light-harvesting Hybrid Assemblies

Chemistry (Weinheim an Der Bergstrasse, Germany). Feb, 2012  |  Pubmed ID: 22294513

Light-harvesting hybrids have gained much importance as they are considered as potential mimics for photosynthetic systems. In this Concept article we introduce the design concepts involved in the building up of light-harvesting hybrids; these resemble the well-studied organic-based assemblies for energy transfer. We have structured this article into three parts based on the strategies adopted in the synthesis of hybrid assemblies, as covalent, semicovalent, and noncovalent procedures. Furthermore, the properties and structural features of the hybrids and analogous organic assemblies are compared. We also emphasize the challenges involved in the processability of these hybrid materials for device applications and present our views and results to address this issue through the design of soft-hybrids by a solution-state, noncovalent, self-assembly process.

Increased Intratumoral Neutrophil in Colorectal Carcinomas Correlates Closely with Malignant Phenotype and Predicts Patients' Adverse Prognosis

PloS One. 2012  |  Pubmed ID: 22295111

Substantial evidence suggests that the presence of inflammatory cells plays a critical role in the development and/or progression of human tumors. Neutrophils are the common inflammatory cells in tumors; however, the infiltration of intratumoral neutrophils in colorectal carcinoma (CRC) and its effect on CRC patients' prognosis are poorly understood.

Clinico-Pathological Characteristics of Triple Negative and Non Triple Negative High Grade Breast Carcinomas with and Without Basal Marker (CK5/6 and EGFR) Expression at a Rural Tertiary Hospital in India

Breast Cancer : Basic and Clinical Research. 2012  |  Pubmed ID: 22346359

Aims of the study were to evaluate the expression Cytokeratin 5/6(CK5/6) and Epidermal Growth Factor Receptor (EGFR) among triple negative breast cancers and high grade infiltrating duct carcinomas. Further to probe if triple negative phenotype can be a surrogate marker for basal phenotype and to correlate the expression of basal markers with disease free survivals among triple negative phenotype and high grade infiltrating duct carcinomas.

3,6-Dimethyl-N,N-bis-(1-phenyl-eth-yl)-1,4-dihydro-1,2,4,5-tetra-zine-1,4-dicarboxamide

Acta Crystallographica. Section E, Structure Reports Online. Feb, 2012  |  Pubmed ID: 22347041

In the title mol-ecule, C(22)H(26)N(6)O(2), the central tetra-zine ring exhibits a boat conformation, and the two phenyl rings form a dihedral angle of 88.39 (6)°. In the crystal, weak N-H⋯O and C-H⋯O hydrogen bonds link mol-ecules into layers parallel to the ab plane.

Comparative Evaluation of Autologous Platelet-Rich Fibrin and Platelet-Rich Plasma in the Treatment of Three-Wall Intrabony Defects in Chronic Periodontitis: A Randomized Controlled Clinical Trial

Journal of Periodontology. Feb, 2012  |  Pubmed ID: 22348695

Background: The topical use of platelet concentrates is recent and its efficiency remains controversial. The present study aimed to explore the clinical and radiographical effectiveness of autologous platelet rich fibrin (PRF) and platelet rich plasma (PRP) in treatment of intrabony defects in chronic periodontitis subjects. Material and Methods: 90 intrabony defects were treated either with autologous PRF with open flap debridement or autologous PRP with open flap debridement or open flap debridement alone. Clinical and radiological parameters such as probing depth (PD), clinical attachment level (CAL), intrabony defect depth and % defect fill were recorded at baseline and 9 months postoperatively. Results: Mean PD reduction and CAL gain was greater in PRF (3.77 + 1.19 mm, 3.17 + 1.29 mm) and PRP (3.77 + 1.07 mm, 2.93 + 1.08 mm) groups than control group (2.97 ± 0.93 mm, 2.83 ± 0.91 mm). Furthermore, significantly greater percentage of mean bone fill was found in the PRF (55.41 + 11.39 %) and PRP (56.85 + 14.01 %) compared to control (1.56 ± 15.12 %). Conclusions: Within the limit of the present study, there was similar PD reduction, CAL gain and bone fill at sites treated with PRF or PRP with conventional open flap debridement. Since PRF is less time consuming and less technique sensitive it may seem as the better among the two. However, long term, multicenter randomized, controlled clinical trials will be required to know their clinical and radiographical effects over bone regeneration.

Recurrent Acute Pulmonary Oedema and Cardiac Arrest Secondary to Intermittent Electrical Dyssynchrony: a Role for Cardiac Resynchronization Despite Preserved Left Ventricular Function

European Journal of Heart Failure. Feb, 2012  |  Pubmed ID: 22348898

Recurrent pulmonary oedema with no obvious precipitant can prove difficult to treat in patients with preserved left ventricular (LV) systolic function. This report describes the novel use of cardiac resynchronization therapy (CRT) in the prevention of acute pulmonary oedema precipitated by intermittent electrical dyssynchrony in a patient with preserved LV systolic function.

Inter-sheet-effect-inspired Graphene Sensors: Design, Fabrication and Characterization

Nanotechnology. Mar, 2012  |  Pubmed ID: 22348946

With their sub-nanometer inter-sheet spacing, few-layer graphenes (FLGs) are alignment-free building blocks for nanosensors based on the inter-sheet effects. In this paper, we have tackled the challenges towards batch fabrication of inter-sheet graphene sensors through controlled layer engineering, edge tailoring and selective electrode fabrication on different atomic layers. An oxygen plasma etching (OPE) technique is developed to remove graphene layer by layer, enabling the batch fabrication of FLGs in a controllable fashion because of the faster speed and readiness of patterning of this process as compared to the conventional mechanical exfoliation. Vapor sensing experiments have shown that 'inter-sheet' sensors possess a higher sensitivity than conventional 'intra-sheet' ones. Vapor sensitivity is improved more than two times in normalized resistance changes by taking the 'inter-sheet' design upon exposure to 0.5% ethanol-nitrogen mixture and 500 Pa water vapor environments, respectively. These remarkable improvements can mainly be attributed to the inter-sheet effects such as electron tunneling, chemical doping, physical insertion and enhanced edge effects. Such effects may result from molecule adsorption/desorption, force/displacement, pressure, surface tension or thermal energy, and can potentially remarkably enrich the applicable transduction mechanisms.

Structure and Function of CYP108D1 from Novosphingobium Aromaticivorans DSM12444: an Aromatic Hydrocarbon-binding P450 Enzyme

Acta Crystallographica. Section D, Biological Crystallography. Mar, 2012  |  Pubmed ID: 22349230

CYP108D1 from Novosphingobium aromaticivorans DSM12444 binds a range of aromatic hydrocarbons such as phenanthrene, biphenyl and phenylcyclohexane. Its structure, which is reported here at 2.2 Å resolution, is closely related to that of CYP108A1 (P450terp), an α-terpineol-oxidizing enzyme. The compositions and structures of the active sites of these two enzymes are very similar; the most significant changes are the replacement of Glu77 and Thr103 in CYP108A1 by Thr79 and Val105 in CYP108D1. Other residue differences lead to a larger and more hydrophobic access channel in CYP108D1. These structural features are likely to account for the weaker α-terpineol binding by CYP108D1 and, when combined with the presence of three hydrophobic phenylalanine residues in the active site, promote the binding of aromatic hydrocarbons. The haem-proximal surface of CYP108D1 shows a different charge distribution and topology to those of CYP101D1, CYP101A1 and CYP108A1, including a pronounced kink in the proximal loop of CYP108D1, which may result in poor complementarity with the [2Fe-2S] ferredoxins Arx, putidaredoxin and terpredoxin that are the respective redox partners of these three P450 enzymes. The unexpectedly low reduction potential of phenylcyclohexane-bound CYP108D1 (-401 mV) may also contribute to the low activity observed with these ferredoxins. CYP108D1 appears to function as an aromatic hydrocarbon hydroxylase that requires a different electron-transfer cofactor protein.

Near-Infrared Spectroscopic Monitoring During Cardiopulmonary Exercise Testing Detects Anaerobic Threshold

Pediatric Cardiology. Feb, 2012  |  Pubmed ID: 22349729

Cardiopulmonary exercise testing (CPET) provides assessment of the integrative responses involving the pulmonary, cardiovascular, and skeletal muscle systems. Application of exercise testing remains limited to children who are able to understand and cooperate with the exercise protocol. Near-infrared spectroscopy (NIRS) provides a noninvasive, continuous method to monitor regional tissue oxygenation (rSO2). Our specific aim was to predict anaerobic threshold (AT) during CPET noninvasively using two-site NIRS monitoring. Achievement of a practical noninvasive technology for estimating AT will increase the compatibility of CPET. Patients without structural or acquired heart disease were eligible for inclusion if they were ordered to undergo CPET by a cardiologist. Data from 51 subjects was analyzed. The ventilatory anaerobic threshold (VAT) was computed on [Formula: see text] and respiratory quotient post hoc using the standard V-slope method. The inflection points of the regional rSO2 time-series were identified as the noninvasive regional NIRS AT for each of the two monitored regions (cerebral and kidney). AT calculation made using an average of kidney and brain NIRS matched the calculation made by VAT for the same patient. Two-site NIRS monitoring of visceral organs is a predictor of AT.

Evidence of Bluetongue Virus Serotype 21 (BTV-21) Divergence

Virus Genes. Feb, 2012  |  Pubmed ID: 22350945

Bluetongue virus serotype 21 (BTV-21) was originally isolated from Australia, but has now been reported from India, Indonesia, China and Japan. We report the isolation, and sequencing of BTV-21 from India. The complete ORF sequence of VP2 gene of this isolate showed that it is closely related to recent BTV-21 isolates from Japan (93-94% identity), and distantly related to BTV-21 reference strain (86% identity). Our results, along with the available sequences of Japanese isolates, suggest that the currently circulating BTV-21 strains from India and Japan are divergent from the original strain(s) from Australia and shed light on designing molecular diagnostics for the detection of BTV.

Diurnal Curve After Phacoemulsification in Patients with Pseudoexfoliation Syndrome and Cataract

Seminars in Ophthalmology. Jan, 2012  |  Pubmed ID: 22352815

Purpose: To evaluate the effect of phacoemulsification on the diurnal curve in patients with pseudoexfoliation syndrome. Method: 2052 patients aged 40 years and older attending our OPD services were screened, of whom 62 patients with pseudoexfoliation and associated significant cataract were selected for the study. All underwent a detailed examination including slit lamp examination, IOP, gonioscopy, and fundus examination. Diurnal variation of intraocular pressure was done at baseline and two and four weeks after phacoemulsification with IOL implantation. The IOP differences after surgery were compared and analyzed. Results: All 62 patients underwent successful phacoemulsification with IOL implantation. Anterior chamber IOL was implanted in 2 of the 6 cases with vitreous loss. The peak IOP of the diurnal curve reduced from 26 ± 3.2 mmHg pre surgery to 19 ± 1.2 mmHg, p < 0.01, while the mean baseline IOP reduced from 22 ± 5.3 mmHg to 15 ± 2.1 mmHg at 2 months after cataract extraction, p = 0.02. The IOP fluctuations (max-min IOP difference) in the diurnal curve also flattened significantly post-surgery in eyes with both open and occludable angles, p < 0.01, with the maximum difference observed during the later part of the day in both groups. Conclusions: Early cataract extraction with IOL can smooth out intraocular pressure fluctuations in patients with pseudoexfoliation and associated cataract with open or narrow angles.

Mood Disorder in Association with Moyamoya Disease

Psychiatry and Clinical Neurosciences. Mar, 2012  |  Pubmed ID: 22353330

Vibrational Properties and Phase Transitions in II-VI Materials: Lattice Dynamics, Ab Initio Studies and Inelastic Neutron Scattering Measurements

Journal of Physics. Condensed Matter : an Institute of Physics Journal. Feb, 2012  |  Pubmed ID: 22354098

Inelastic neutron scattering measurements were carried out to determine the phonon density of states of ZnSe and interpreted with lattice dynamical computations (ab initio as well as a potential model). Calculations are also reported for other II-VI compounds, ZnTe and ZnS. Vibrational (phonon spectra and Grüneisen parameters), and thermal (negative thermal expansion and non-Debye specific heat) properties have been calculated and found to be in good agreement with available experimental data. This model has been further employed to study the pressure-induced solid-solid phase transitions exhibited by these compounds and the results have been compared with experimental data. Total energy calculations for zincblende and SC16 phases of ZnSe were carried out employing the pseudopotential approach under the local density approximation (LDA) as well as the generalized gradient approximation (GGA). The density functional perturbation theory is applied to study the vibrational properties of the zincblende and SC16 phases of ZnSe. An investigation of the pressure dependence of the phonon frequencies shows that the existence of the (experimentally undetected) SC16 phase as a thermodynamically stable high pressure phase is impeded due to dynamical instabilities. A detailed investigation of the polarization of phonons of different energies for the various phases of these compounds indicates that in the case of the zincblende phase the low energy modes are librational, while in the rocksalt phase the low energy modes are bending modes. Further, in ZnTe the low energy bending modes display a larger amplitude of bending than that in ZnSe and ZnS.

Inhibition of Autophagy Ameliorates Acute Lung Injury Caused by Avian Influenza A H5N1 Infection

Science Signaling. 2012  |  Pubmed ID: 22355189

The threat of a new influenza pandemic has existed since 1997, when the highly pathogenic H5N1 strain of avian influenza A virus infected humans in Hong Kong and spread across Asia, where it continued to infect poultry and people. The human mortality rate of H5N1 infection is about 60%, whereas that of seasonal H1N1 infection is less than 0.1%. The high mortality rate associated with H5N1 infection is predominantly a result of respiratory failure caused by acute lung injury; however, how viral infection contributes to this disease pathology is unclear. Here, we used electron microscopy to show the accumulation of autophagosomes in H5N1-infected lungs from a human cadaver and mice, as well as in infected A549 human epithelial lung cells. We also showed that H5N1, but not seasonal H1N1, induced autophagic cell death in alveolar epithelial cells through a pathway involving the kinase Akt, the tumor suppressor protein TSC2, and the mammalian target of rapamycin. Additionally, we suggest that the hemagglutinin protein of H5N1 may be responsible for stimulating autophagy. When applied prophylactically, reagents that blocked virus-induced autophagic signaling substantially increased the survival rate of mice and substantially ameliorated the acute lung injury and mortality caused by H5N1 infection. We conclude that the autophagic cell death of alveolar epithelial cells likely plays a crucial role in the high mortality rate of H5N1 infection, and we suggest that autophagy-blocking agents might be useful as prophylactics and therapeutics against infection of humans by the H5N1 virus.

Emergence of Distinct Brome Mosaic Virus Recombinants is Determined by the Polarity of the Inoculum RNA

Journal of Virology. Feb, 2012  |  Pubmed ID: 22357282

Despite overwhelming interest on the impact exerted by recombination during evolution of RNA viruses, the relative contribution of the polarity of inoculum templates remains poorly understood. Here, by agro-infiltrating Nicotiana benthamiana leaves, we show that Brome mosaic virus (BMV) replicase is competent to initiate (+)-strand synthesis on an ectopically expressed RNA3 (-)-strand and faithfully complete the replication cycle. Consequently, we sought to examine the role of RNA polarity in BMV recombination by expressing a series of replication-defective mutants of BMV RNA3 in (+) or (-)-polarity. Temporal analysis of progeny sequences revealed that the genetic makeup of the primary recombinant pool is determined by the polarity of the inoculum template. When the polarity of the inoculum template was (+)-strand, the recombinant pool accumulated during early phases of replication was a mixture of non-homologous recombinants. These are longer than the inoculum template length and a nascent 3' un-translated region (UTR) of wild type (wt) RNA1 or RNA2 was added to the input mutant RNA3 3' UTR due to end-to-end template switching by BMV replicase during (-)-strand synthesis. In contrast, when the polarity of the inoculum was (-)-strand, the progeny contained a pool of native length homologous recombinants generated by template switching of BMV replicase with nascent UTR from wt RNA1 or RNA2 during (+)-strand synthesis. Repair of a point mutation caused by polymerase error occurred only when the polarity of the inoculum template was (+)-strand. These results contribute to explain the functional role of RNA polarity in recombination mediated by copy-choice mechanisms.

Human Hepatocellular Carcinoma in a Mouse Model: Assessment of Tumor Response to Percutaneous Ablation by Using Glyceraldehyde-3-phosphate Dehydrogenase Antagonists

Radiology. Mar, 2012  |  Pubmed ID: 22357885

Purpose: To characterize tumor response to percutaneous injection of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) antagonists in a mouse model of human hepatocellular carcinoma (HCC). Materials and Methods: Animal experiments were approved by the Johns Hopkins University Animal Care and Use Committee. Luciferase (luc) gene-expressing Hep3B tumor-bearing athymic nude mice were randomly divided into four groups of six mice each. Tumor-specific GAPDH inhibition was achieved by using percutaneous injection of GAPDH antagonists-3-bromopyruvate (3-BrPA) or GAPDH-specific short hairpin RNA (shRNA). Tumor response to treatment was assessed by using bioluminescence imaging and analysis of GAPDH function and apoptotic markers (caspase-3, caspase-9, and positive staining for terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphospate nick end labeling). HCC samples from 34 patients were obtained from the Johns Hopkins tumor bank, as approved by the Institutional Review Board, for GAPDH expression analysis. Statistical analysis was performed by using a two-sample t test or Spearman rank correlation coefficient. Results: In vitro, 3-BrPA affected Hep3B cell viability (half maximal inhibitory concentration = 0.15 mmol/L), and GAPDH shRNA suppressed (45.5%) colony formation. In vivo, percutaneous injection of GAPDH antagonists into luc-Hep3B tumors decreased bioluminescence imaging signal and viability (3-BrPA, P < .0001; GAPDH shRNA, P = .03). The 3-BrPA treatment primarily inhibited GAPDH activity (74.5%) compared with its expression (34.3%), whereas GAPDH shRNA inhibited both activity (60.6%) and expression (44.4%). Targeted inhibition of GAPDH by using 3-BrPA or shRNA induced apoptosis. HCC samples from patients demonstrated a strong correlation between GAPDH upregulation and the proto-oncogene c-jun expression (r = 0.543, P = .003). Conclusion: Percutaneous injection of GAPDH antagonists induces apoptosis and blocks Hep3B tumor progression, which demonstrates the therapeutic potential of targeting GAPDH in human HCC. © RSNA, 2012.

Primary Pulmonary Lymphoepithelioma-like Carcinoma: Fifty-two Patients with Long-term Follow-up

Cancer. Feb, 2012  |  Pubmed ID: 22359203

BACKGROUND: Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare kind of cancer. METHODS: In this study, the authors evaluated 52 patients with pulmonary LELC who had long-term follow-up. Clinical characteristics, tumor markers, epidermal growth factor receptor (EGFR) mutation status, treatments, and outcomes were analyzed. RESULTS: Pulmonary LELC mostly affected young, nonsmoking patients. Most patients were in early or locally advanced stages and received multimodality treatment. Serum levels of neuron-specific enolase and cytokeratin 19 fragment 21-1 were elevated in 11 of 20 patients and 10 of 16 patients, respectively. Mutational analysis of EGFR was done in 11 patients, and all were wild type. The median overall survival (OS) for all the patients was not reached, and the 2-year and 5-year OS rate was 88% and 62%, respectively. The patients with early tumor stage, normal serum lactate dehydrogenase level, normal serum albumin level, without lymph node metastasis, and those who underwent complete resection had significantly better OS (P < .05); and the serum albumin level was an independent prognostic factor in a Cox regression model (P = .005). For all patients who underwent complete resection, whether or not they received adjuvant chemotherapy did not affect OS (P > .05); whereas, for patients with stage IIIA disease who underwent complete resection, adjuvant chemotherapy was correlated with a significantly better prognosis (P < .05). CONCLUSIONS: Pulmonary LELC obviously is a distinct entity of lung cancer that has a better prognosis, because patients with LELC can receive multimodality treatment, and LELC has biologic behavior similar to that of nasopharyngeal carcinoma. The current results indicated that future collaborative efforts are needed to determine the optimal treatment methods for this uncommon malignancy. Cancer 2012;. © 2012 American Cancer Society.

A Measure of the Promiscuity of Proteins and Characteristics of Residues in the Vicinity of the Catalytic Site That Regulate Promiscuity

PloS One. 2012  |  Pubmed ID: 22359655

Promiscuity, the basis for the evolution of new functions through 'tinkering' of residues in the vicinity of the catalytic site, is yet to be quantitatively defined. We present a computational method Promiscuity Indices Estimator (PROMISE) - based on signatures derived from the spatial and electrostatic properties of the catalytic residues, to estimate the promiscuity (PromIndex) of proteins with known active site residues and 3D structure. PromIndex reflects the number of different active site signatures that have congruent matches in close proximity of its native catalytic site, the quality of the matches and difference in the enzymatic activity. Promiscuity in proteins is observed to follow a lognormal distribution (μ = 0.28, σ = 1.1 reduced chi-square = 3.0E-5). The PROMISE predicted promiscuous functions in any protein can serve as the starting point for directed evolution experiments. PROMISE ranks carboxypeptidase A and ribonuclease A amongst the more promiscuous proteins. We have also investigated the properties of the residues in the vicinity of the catalytic site that regulates its promiscuity. Linear regression establishes a weak correlation (R(2)∼0.1) between certain properties of the residues (charge, polar, etc) in the neighborhood of the catalytic residues and PromIndex. A stronger relationship states that most proteins with high promiscuity have high percentages of charged and polar residues within a radius of 3 Å of the catalytic site, which is validated using one-tailed hypothesis tests (P-values∼0.05). Since it is known that these characteristics are key factors in catalysis, their relationship with the promiscuity index cross validates the methodology of PROMISE.

Fabrication of Unipolar Graphene Field-Effect Transistors by Modifying Source and Drain Electrode Interfaces with Zinc Porphyrin

ACS Applied Materials & Interfaces. Feb, 2012  |  Pubmed ID: 22332817

We report a unipolar operation in reduced graphene oxide (RGO) field-effect transistors (FETs) via modification of the source/drain (S/D) electrode interfaces with self-assembled monolayers (SAMs) of 5-(4-hydroxyphenyl)-10,15,20-tri-(p-tolyl) zinc(II) porphyrin (Zn(II)TTPOH) molecules. The dipolar Zn(II)TTPOH molecules at the RGO/platinum (Pt) S/D interface results in an increase of the electron injection barrier and a reduction of the hole-injection barrier. Using dipole measurements from Kelvin probe force microscopy and highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) calculations from cyclic voltammetry, the electron and hole injection barriers were calculated to be 2.2 and 0.11 eV, respectively, indicating a higher barrier for electrons, compared to that of holes. A reduced gate modulation in the electron accumulation regime in RGO devices with SAM shows that unipolar RGO FETs can be attained using a low-cost, solution-processable fabrication technique.

Hemocompatibility and Macrophage Response of Pristine and Functionalized Graphene

Small (Weinheim an Der Bergstrasse, Germany). Feb, 2012  |  Pubmed ID: 22334378

Graphene and its derivatives are being proposed for several important biomedical applications including drug delivery, gene delivery, contrast imaging, and anticancer therapy. Most of these applications demand intravenous injection of graphene and hence evaluation of its hemocompatibility is an essential prerequisite. Herein, both pristine and functionalized graphene are extensively characterized for their interactions with murine macrophage RAW 264.7 cells and human primary blood components. Detailed analyses of the potential uptake by macrophages, effects on its metabolic activity, membrane integrity, induction of reactive oxygen stress, hemolysis, platelet activation, platelet aggregation, coagulation cascade, cytokine induction, immune cell activation, and immune cell suppression are performed using optimized protocols for nanotoxicity evaluation. Electron microscopy, confocal Raman spectral mapping, and confocal fluorescence imaging studies show active interaction of both the graphene systems with macrophage cells, and the reactive oxygen species mediated toxicity effects of hydrophobic pristine samples are significantly reduced by surface functionalization. In the case of hemocompatibility, both types of graphene show excellent compatibility with red blood cells, platelets, and plasma coagulation pathways, and minimal alteration in the cytokine expression by human peripheral blood mononuclear cells. Further, both samples do not cause any premature immune cell activation or suppression up to a relatively high concentration of 75 μg mL(-1) after 72 h of incubation under in vitro conditions. This study clearly suggests that the observed toxicity effects of pristine graphene towards macrophage cells can be easily averted by surface functionalization and both the systems show excellent hemocompatibility.

Accuracy of Intraocular Lens Power Calculation Formulae in Children Less Than Two Years

American Journal of Ophthalmology. Feb, 2012  |  Pubmed ID: 22336039

PURPOSE: To assess the accuracy of IOL power calculation formulae in children less than 2 years of age. DESIGN: Retrospective, comparative study, comprising of 128 eyes of 84 children. METHODS: We analyzed records of children less than 2 years with congenital cataract who underwent primary IOL implantation. Data were analyzed for prediction error using the 4 commonly used IOL power calculation formulae. We calculated the absolute prediction error with each of the formulae and the formula that gave least variability was determined. The formula that gave the best prediction error was determined. RESULTS: Mean age at surgery was 11.7 ± 6.2 months. Absolute prediction error was found to be 2.27 ± 1.69 diopters (D) with SRK II, 3.23 ± 2.24 D with SRK T, 3.62 ± 2.42 D with Holladay, and 4.61 ± 3.12 D with Hoffer Q. The number of eyes with absolute prediction error within 0.5 D was 27 (21.1%) with SRK II, 8 (6.3%) with SRK T, 12 (9.4%) with Holladay, and 5 (3.9%) with Hoffer Q. Comparison between different formulae showed that the absolute prediction error with SRK II formula was significantly better than with other formulae (P < .001). Prediction error with SRK II formula was not affected by any factor such as age (P = .31), keratometry (P = .32), and axial length (P = .27) of the patient. Axial length influenced the absolute prediction error with Holladay (P = .05) and Hoffer Q formulae (P = .002). Mean keratometry influenced prediction error (P = .03) with SRK T formula. CONCLUSION: Although absolute prediction error tends to remain high with all present IOL power calculation formulae, SRK II was the most predictable formula in our series.

A Cost Study of Postoperative Cell Salvage in the Setting of Elective Primary Hip and Knee Arthroplasty

Transfusion. Feb, 2012  |  Pubmed ID: 22339139

BACKGROUND: The increasing costs, limited supply, and clinical risks associated with allogeneic blood transfusion have prompted investigation into autologous blood management strategies, such as postoperative red blood cell (RBC) salvage. This study provides a cost comparison of transfusing washed postoperatively salvaged RBCs using an orthopedic perioperative autotransfusion device (OrthoPat, Haemonetics Corporation) versus unwashed shed blood and banked allogeneic blood. STUDY DESIGN AND METHODS: Cell salvage data were retrospectively reviewed for a sample of 392 patients who underwent primary hip or knee arthroplasty. Mean unit costs were calculated for washed salvaged RBCs, equivalent units of unwashed shed blood, and therapeutically equivalent volumes of allogeneic RBCs. RESULTS: No initial capital investment was required for the establishment of the postoperative cell salvage program. For patients undergoing total knee arthroplasty (TKA), the mean unit costs for washed postoperatively salvaged cells, unwashed shed blood, and allogeneic banked blood were $758.80, $474.95, and $765.49, respectively. In patients undergoing total hip arthroplasty (THA), the mean unit costs for washed postoperatively salvaged cells, unwashed shed blood, and allogeneic banked blood were $1827.41, $1167.41, and $2609.44, respectively. CONCLUSION: This analysis suggests that transfusing washed postoperatively salvaged cells using the OrthoPat device is more costly than using unwashed shed blood in both THA and TKA. When compared to allogeneic transfusion, washed postoperatively salvaged cells carry a comparable cost in TKA, but potentially represent a significant savings in patients undergoing THA. Sensitivity analysis suggests that in the case of TKA, however, cost comparability exists within a narrow range of units collected and infused.

Laparoscopic Cryotherapy for Renal Tumours

BJU International. Mar, 2012  |  Pubmed ID: 22339994

Chemistry Experiments with Elemental Metals - Fuel for the Minds, Formula for Disaster?

Burns : Journal of the International Society for Burn Injuries. Feb, 2012  |  Pubmed ID: 22342174

Burden of Invasive Cervical Cancer in North Carolina

Preventive Medicine. Feb, 2012  |  Pubmed ID: 22342290

OBJECTIVE: Cervical cancer causes over 4000 deaths yearly in the United States, although highly preventable through vaccination, screening, and early treatment. We aimed to determine demographic correlates for cervical cancer in North Carolina to identify target populations for interventions and to create a framework for state-level analyses. METHOD: Data on all reported invasive cervical cancer cases from 1998 to 2007 were obtained from the North Carolina Central Cancer Registry. Age-adjusted incidence and mortality rates were estimated using population data from the National Center for Health Statistics. RESULTS: Cervical cancer incidence and mortality rates varied greatly by county and were inversely associated with county prosperity. Hispanic women had the highest incidence rate, black women the highest mortality rate, although white women accounted for most cases. Incidence rates remained fairly steady above age 35 and mortality rates steadily increased with age. A later stage at diagnosis was more common for older women and for women without private insurance. CONCLUSION: Registry-based assessment illustrates the economic, racial, and age disparities associated with cervical cancer. This localized focus on demographic correlates is an important step toward eliminating this preventable disease and offers a template for cervical cancer prevention programs in other states.

Hedgehog-Gli Pathway Activation During Kidney Fibrosis

The American Journal of Pathology. Feb, 2012  |  Pubmed ID: 22342522

The Hedgehog (Hh) signaling pathway regulates tissue patterning during development, including patterning and growth of limbs and face, but whether Hh signaling plays a role in adult kidney remains undefined. In this study, using a panel of hedgehog-reporter mice, we show that the two Hh ligands (Indian hedgehog and sonic hedgehog ligands) are expressed in tubular epithelial cells. We report that the Hh effectors (Gli1 and Gli2) are expressed exclusively in adjacent platelet-derived growth factor receptor-β-positive interstitial pericytes and perivascular fibroblasts, suggesting a paracrine signaling loop. In two models of renal fibrosis, Indian Hh ligand was upregulated with a dramatic activation of downstream Gli effector expression. Hh-responsive Gli1-positive interstitial cells underwent 11-fold proliferative expansion during fibrosis, and both Gli1- and Gli2-positive cells differentiated into α-smooth muscle actin-positive myofibroblasts. In the pericyte-like cell line 10T1/2, hedgehog ligand triggered cell proliferation, suggesting a possible role for this pathway in the regulation of cell cycle progression of myofibroblasts progenitors during the development of renal fibrosis. The hedgehog antagonist IPI-926 abolished Gli1 induction in vivo but did not decrease kidney fibrosis. However, the transcriptional induction of Gli2 was unaffected by IPI-926, suggesting the existence of smoothened-independent Gli activation in this model. This study is the first detailed description of paracrine hedgehog signaling in adult kidney, which indicates a possible role for hedgehog-Gli signaling in fibrotic chronic kidney disease.

Has Kahlbaum Syndrome Disappeared or is It Underdiagnosed?: Reexamining the Nosology of Catatonia

The Journal of ECT. Mar, 2012  |  Pubmed ID: 22343585

ABSTRACT: In contemporary psychiatric classification such as the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, and International Classification of Diseases, 10th Revision, catatonia is classified as a subtype of schizophrenia and not as an independent disorder. However, catatonia does not seem to obey nosological boundaries and is seen with both affective and nonaffective psychoses. We conducted a chart review of patients to examine the nosological status of catatonia. Our data suggest that catatonia is a syndrome of varied manifestation possibly related to both affective and nonaffective psychoses with a subgroup independent of both. Further prospective studies examining the natural course are needed, which could have significant implications on future classificatory systems.

Graded Compression and Power Doppler Ultrasonography Versus Endoscopy to Assess Paediatric Crohn Disease Activity Pre- and Posttreatment

Journal of Pediatric Gastroenterology and Nutrition. Mar, 2012  |  Pubmed ID: 22343835

: The aim of this study was to assess whether power Doppler ultrasound (PDU) can serve as a reliable replacement for endoscopy in follow-up assessment of disease activity in children with Crohn disease.

Evaluating The Bite of BARC

Circulation. Feb, 2012  |  Pubmed ID: 22344038

Therapeutic options for patients with acute coronary syndrome (ACS) and those undergoing percutaneous coronary intervention (PCI) have evolved significantly over the past decade. In the era when there were limited antithrombotic choices, reduction of ischemic events was the primary goal regardless of the risk of bleeding that was associated with the use of antiplatelet and anticoagulant therapies. In the current era, clinicians are faced with five oral antiplatelet options (aspirin, ticlopidine, clopidogrel, prasugrel, ticagrelor), three intravenous antiplatelet agents (abciximab, eptifibatide, tirofiban), four anticoagulants (unfractionated heparin, low molecular weight heparin, bivalirudin, fondaparinux), and potentially additional oral anticoagulants for long-term secondary prevention(1). In general, the iterations in antithrombotic drugs have been directed at achieving greater potency; however, some agents, like fondaparinux and bivalirudin, were developed specifically in the context of maintaining antithrombotic efficacy but with better safety (i.e., lower bleeding risk)(2,3).The focus on bleeding risk is a relatively new development, and is likely driven by the robust literature demonstrating an association between bleeding during the management of ACS or in the setting of PCI and subsequent short- and long-term adverse outcomes such as myocardial infarction (MI), stroke, stent thrombosis, and death(4,5 )(SELECT FULL TEXT TO CONTINUE).

Evaluation of (R)-(-)-α-methoxy Phenyl Acetic Acid As a Chiral Shift Reagent for Resolution and Determination of R and S Enantiomers of Modafinil in Bulk Drugs and Formulations by (1) H NMR Spectroscopy

Chirality. Feb, 2012  |  Pubmed ID: 22344605

(R)-(-)-α-Methoxy phenyl acetic acid, (S)-(-)-1,1'-(2-naphthol), and (R)-(+)-α-methoxy-α-trifluoromethyl phenyl acetic acid were evaluated as chiral shift reagents (CSRs) for (1) H NMR spectroscopic resolution and determination of R and S enantiomers of modafinil (MDL) in bulk drugs and formulations. Effects of the nature of CSR and the weight ratio of substrate to shift reagent on enantiomeric discrimination were investigated. Intramolecular and intermolecular hydrogen bonding interactions between the drug and the CSR seem to be the driving force for desired resolution. A mechanism was proposed to explain the interactions between (R, S)-enantiomers of MDL and (R)-(-)-α-methoxy phenyl acetic acid. The method was validated and applied successfully to determine the enantiomeric purity of MDL in tablet formulations. Chirality, 2012. © 2012 Wiley Periodicals, Inc.

A Selenium Analogue of Firefly D-Luciferin with Red-Shifted Bioluminescence Emission

Angewandte Chemie (International Ed. in English). Feb, 2012  |  Pubmed ID: 22344705

A selenium analogue of amino-D-luciferin, aminoseleno-D-luciferin, is synthesized and shown to be a competent substrate for the firefly luciferase enzyme. It has a red-shifted bioluminescence emission maximum at 600 nm and is suitable for bioluminescence imaging studies in living subjects.

The Chameleon-Like Nature of Zwitterionic Micelles: The Effect of Ionic Liquid Addition on the Properties of Aqueous Sulfobetaine Micelles

Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry. Feb, 2012  |  Pubmed ID: 22344856

We used fluorescence probing, ζ potentials, and dynamic light scattering measurements to study the interactions between the zwitterionic surfactant N-hexadecyl-N,N-dimethylammonio-1-propanesulfonate (SB-16) and three ionic liquids (ILs), 1-ethyl-3-methylimidazolium ethylsulfate ([C(2) mim][C(2) SO(4) ]), 1-ethyl-3-methylimidazolium n-butylsulfate ([C(2) mim][C(4) SO(4) ]), and 1-ethyl-3-methylimidazolium n-hexylsulfate ([C(2) mim][C(6) SO(4) ]). The three ILs have the same cationic part and their anionic parts differ only in the length of the alkyl chain. The aim of our work is to offer a comparative study and establish the role of the alkyl chain length of the anion of ILs on 1) the incorporation of these anions in the zwitterionic micelles of SB-16 (selectivity of anions) and 2) the physicochemical properties of aqueous solutions of SB-16. Results show that, at lower concentrations (i.e. ≤20 mM), the different ILs modify the properties of the aqueous SB-16 solution in similar manner. All of them bring about a decrease in the critical micelle concentration (CMC) and also in size, and increase the aggregation number of the SB-16 micelles; these effects are more dramatic when [C(2) mim][C(6) SO(4) ] is used as the additive rather than [C(2) mim][C(4) SO(4) ] and [C(2) mim][C(2) SO(4) ]. It is proposed that, in case of [C(2) mim][C(6) SO(4) ], the presence of a hexyl chain on the hexylsulfate ion allows the ion to align itself with the tail part of SB-16, whereas, in the case of [C(2) mim][C(2) SO(4) ], the presence of ethyl chain in the ethylsulfate ion is not sufficient to bring about a similar alignment of the ethylsulfate anion with the tail part of SB-16. This difference in the location of the anions of the ILs is responsible for the different behavior of the ILs.

[Comparison of Gene Expression Between Naturally Occurring and Diet-induced T2DM in Cynomolgus Monkeys]

Dong Wu Xue Yan Jiu = Zoological Research / "Dong Wu Xue Yan Jiu" Bian Ji Wei Yuan Hui Bian Ji. Feb, 2012  |  Pubmed ID: 22345013

To explore pathological alteration of T2DM in cynomolgus monkeys, gene expression profiles of peripheral blood leukocytes from spontaneous and diet-induced T2DM models was analyzed using quantitative real-time PCR. Among 36 T2DM associated genes tested, 19 genes (including G6PC, CCR2B, CTLA4) displayed a similar expression pattern in both spontaneous and diet-induced T2DM models and were significantly up-regulated or down-regulated compared to controls. Interestingly, expression abundance of all up-regulated genes in the diet-induced T2DM was stronger, although not significantly, than spontaneous models, indicating diet-induced T2DM in monkeys should be a reliable research model for changes in gene expression. The characteristic gene expression pattern obtained here may be useful for the clinical diagnosis of T2DM.

Reply to Jarvis

European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery. Mar, 2012  |  Pubmed ID: 22345206

Portal-Large Terminase Interactions of the Bacteriophage T4 DNA Packaging Machine Implicates a Molecular Lever Mechanism for Coupling ATPase to DNA Translocation

Journal of Virology. Feb, 2012  |  Pubmed ID: 22345478

DNA packaging by double stranded DNA bacteriophages and herpes viruses is driven by a powerful molecular machine assembled at the portal vertex of the empty prohead. The phage T4 packaging machine consists of three components: dodecameric portal (gp20), pentameric large terminase motor (gp17), and 11- or 12-meric small terminase (gp16). These components dynamically interact and orchestrate a complex series of reactions to produce a DNA-full head containing one viral genome per head. Here, we analyzed the interactions between the portal and motor proteins using a direct binding assay, mutagenesis, and structural analyses. Our results show that a portal binding site is located in the ATP-hydrolysis-controlling subdomain II of gp17. Mutations at key residues of this site lead to temperature sensitive or null phenotypes. A conserved helix-turn-helix (HLH) that is part of this site interacts with the portal. A recombinant HLH peptide competes with gp17 for portal binding and blocks DNA translocation. The helices apparently provide specificity to capture the cognate prohead whereas the loop residues communicate portal interaction to the ATPase center. These observations lead to a hypothesis in which a unique HLH-portal interaction in the symmetrically mismatched complex acts as a lever to position the arginine finger and trigger ATP hydrolysis. Transiently connecting the critical parts of the motor; subdomain I (ATP binding), subdomain II (controlling ATP hydrolysis), and C-domain (DNA movement), the portal-motor interactions might ensure tight coupling between ATP hydrolysis and DNA translocation.

An Understanding of the Modulation of Photophysical Properties of Curcumin Inside a Micelle Formed by an Ionic Liquid: A New Possibility of Tunable Drug Delivery System

The Journal of Physical Chemistry. B. Feb, 2012  |  Pubmed ID: 22324726

Present study reveals the modulation of photophysical properties of curcumin, a important drug for numerous reasons inside micellar environment formed by a surfactant-like ionic liquid (IL-micelle) in aqueous solution. Higher stability of the drug inside IL-micelle in absence and in presence of a simple salt (sodium chloride) as well as considerably large partition coefficient ( = 8.59 103) to micellar phase from water make this system as a well behaved drug loading vehicle. Remarkable change in fluorescence intensity with a strong blue-shift implies that the gradual perturbation of intramolecular hydrogen bond (H-bond) present within the keto-enol group of curcumin along with considerable formation of intermolecular H-bond between curcumin and headgroup of surfactant-like IL. Very fast nonradiative decay channels in curcumin mainly caused by the Excited State Intramolecular Proton Transfer (ESIPT) is thus depleted remarkably in presence of IL-micelle of reduced polarity and as a result of restricted rotational and vibrational degrees of freedom when bound to the micelle. Moreover, time-resolved results confirm that not only the keto-enol group of curcumin is playing here but also the phenolic hydroxyl groups are also responsible for such modulation in photophysical properties. From thermodynamic point of view, our system shows good correlation with its stability parameters (higher binding constant with very less hydrolytic degradation rate ~1%) and higher negative value of binding enthalpy of interaction (-∆H) than total free energy change (-∆G) implies that the nature of binding interaction is enthalpy driven not entropy alone. Summarizing all the above observations we have concluded that the modulation of the intramolecular proton transfer is due to presence of both intermolecular proton transfer as well as strong hydrophobic interaction between curcumin and the IL-micelle.

Pretreatment with Anti-VEGF Therapy May Exacerbate Inflammation in Experimental Acute Colitis

Journal of Pediatric Surgery. Feb, 2012  |  Pubmed ID: 22325388

Our previous investigations of angiogenesis in inflammatory bowel disease showed that vascular endothelial growth factor (VEGF) blockade reduced colonic neovascularization and inflammation. We hypothesized that pretreatment with bevacizumab, a monoclonal anti-VEGF antibody, would attenuate the severity of angiogenesis and inflammation in a murine model of colitis.

Comparison of Antibiotic Susceptibility Patterns in Pseudomonas Aeruginosa Isolated from Adult Patients with Cystic Fibrosis (CF) with Invasive Pseudomonas Aeruginosa from Non-CF Patients

Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society. Feb, 2012  |  Pubmed ID: 22325689

Interleukin-4 Production by Follicular Helper T Cells Requires the Conserved Il4 Enhancer Hypersensitivity Site V

Immunity. Feb, 2012  |  Pubmed ID: 22326582

Follicular helper T cells (Tfh cells) are the major producers of interleukin-4 (IL-4) in secondary lymphoid organs where humoral immune responses develop. Il4 regulation in Tfh cells appears distinct from the classical T helper 2 (Th2) cell pathway, but the underlying molecular mechanisms remain largely unknown. We found that hypersensitivity site V (HS V; also known as CNS2), a 3' enhancer in the Il4 locus, is essential for IL-4 production by Tfh cells. Mice lacking HS V display marked defects in type 2 humoral immune responses, as evidenced by abrogated IgE and sharply reduced IgG1 production in vivo. In contrast, effector Th2 cells that are involved in tissue responses were far less dependent on HS V. HS V facilitated removal of repressive chromatin marks during Th2 and Tfh cell differentiation and increased accessibility of the Il4 promoter. Thus, Tfh and Th2 cells utilize distinct but overlapping molecular mechanisms to regulate Il4, a finding with important implications for understanding the molecular basis of allergic diseases.

The Triple-P Procedure As a Conservative Surgical Alternative to Peripartum Hysterectomy for Placenta Percreta

International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. Feb, 2012  |  Pubmed ID: 22326782

The reported maternal mortality for morbidly adherent placenta ranges from 7% to 10% worldwide. Current treatment modalities for this potentially life-threatening condition include radical approaches such as elective peripartum hysterectomy with or without bowel/bladder resection or ureteric re-implantation (for placenta percreta infiltrating these organs), and conservative measures such as compression sutures with balloon tamponade and the placenta remaining in situ. However, both conservative and radical measures are associated with significant maternal morbidity and mortality. The present article describes the Triple-P procedure-which involves perioperative placental localization and delivery of the fetus via transverse uterine incision above the upper border of the placenta; pelvic devascularization; and placental non-separation with myometrial excision and reconstruction of the uterine wall-as a safe and effective alternative to conservative management or peripartum hysterectomy.

Unusual Differential Diagnosis of Common Arterial Trunk

Pediatric Cardiology. Feb, 2012  |  Pubmed ID: 22327230

Common arterial trunk is relatively a straightforward diagnosis on echocardiography. We describe a neonate who was referred to our centre as a case of common arterial trunk but on evaluation was found to have pulmonary atresia with ventricular septal defect and aortopulmonary window, for which he underwent repair with Barbero-Marcial technique. These two conditions differ anatomically and embryologically, and careful echocardiographic evaluation will help in diagnosis and appropriate management.

Halofuginone and Other Febrifugine Derivatives Inhibit Prolyl-tRNA Synthetase

Nature Chemical Biology. 2012  |  Pubmed ID: 22327401

Febrifugine, the bioactive constituent of one of the 50 fundamental herbs of traditional Chinese medicine, has been characterized for its therapeutic activity, though its molecular target has remained unknown. Febrifugine derivatives have been used to treat malaria, cancer, fibrosis and inflammatory disease. We recently demonstrated that halofuginone (HF), a widely studied derivative of febrifugine, inhibits the development of T(H)17-driven autoimmunity in a mouse model of multiple sclerosis by activating the amino acid response (AAR) pathway. Here we show that HF binds glutamyl-prolyl-tRNA synthetase (EPRS), inhibiting prolyl-tRNA synthetase activity; this inhibition is reversed by the addition of exogenous proline or EPRS. We further show that inhibition of EPRS underlies the broad bioactivities of this family of natural product derivatives. This work both explains the molecular mechanism of a promising family of therapeutics and highlights the AAR pathway as an important drug target for promoting inflammatory resolution.

IL28B Genetic Variants and Gender Are Associated with Spontaneous Clearance of Hepatitis C Virus Infection

Journal of Viral Hepatitis. Mar, 2012  |  Pubmed ID: 22329371

Summary.  Single nucleotide polymorphisms (SNPs) near the IL28B gene have been shown to be associated with response to treatment for chronic hepatitis C and also with spontaneous clearance of hepatitis C virus (HCV) infection. We analysed the association between IL28B genetic variants and spontaneous clearance of HCV infection in 376 HCV-infected Chinese paid plasma donors. Genotyping of eight SNPs near the IL28B region was performed by the iPLEX system (MassARRAY(®) SNP Genotyping; Sequenom) in all donors, and sequencing was performed on all 80 donors who cleared HCV and on 160 of 296 donors who did not clear HCV to validate the genotypes. Eighty (21.3%) donors spontaneously cleared HCV. Four SNPs were significantly associated with spontaneous HCV clearance: rs8099917 TT (vs GT), rs8105790 TT (vs CT), rs12980275 AA (vs AG) and rs10853728 CC (vs CG or GG) with OR (95% CI) 15.27 (2.07-112.50), 14.88 (2.02-109.72), 7.92 (1.88-33.32) and 2.32 (1.22-4.42) respectively. No association between the other four IL28B SNPs including rs12979860 and spontaneous HCV clearance was found. Women had a higher rate of spontaneous HCV clearance than men [56/213 (26.3%) vs 24/163 (14.6%), P = 0.007], and this was true even after stratification for IL28B genotypes with OR of 1.9-2.2 among those with favourable genotypes. Our results confirmed that IL28B polymorphism is associated with spontaneous clearance of HCV in Chinese subjects, but the SNPs that predict HCV clearance in Chinese subjects were different from those reported in Caucasians. Women were more likely to clear HCV infection regardless of IL28B genotypes.

Designing a New Strategy for the Formation of IL-in-Oil Microemulsions

The Journal of Physical Chemistry. B. Feb, 2012  |  Pubmed ID: 22329703

Due to the increasing applicability of ionic liquids (ILs) as different components of microemulsions (as the polar liquid, the oil phase, and the surfactant), it would be advantageous to devise a strategy by which we can formulate a microemulsion of our own interest. In this paper, we have shown how we can replace water from water-in-oil microemulsions by ILs to produce IL-in-oil microemulsions. We have synthesized AOT-derived surface-active ionic liquids (SAILs) which can be used to produce a large number of IL-in-oil microemulsions. In particular, we have characterized the phase diagram of the [C(4)mim][BF(4)]/[C(4)mim][AOT]/benzene ternary system at 298 K. We have shown the formation of IL-in-oil microemulsions using the dynamic light scattering (DLS) technique and using methyl orange (MO), betaine 30, and coumarin-480 (C-480) as probe molecules.

Study of Clinical, Biochemical and Immunological Factors Determining Stability of Disease in Patients with Generalized Vitiligo Undergoing Melanocyte Transplantation

The British Journal of Dermatology. Feb, 2012  |  Pubmed ID: 22329760

Background:  "Stability" is considered as the most important parameter before performing any melanocyte transplantation procedure in vitiligo, however, current criteria rely on history given by the patients. Objective:  This study was undertaken to determine clinical, biochemical and immunological factors determining stability of disease in patients with generalized vitiligo to facilitate better patient selection for melanocyte transplantation and to understand immunological mechanisms for disease activity. Methods:  Thirty three patients with generalized vitiligo with <10% body surface area involved were allocated into 3 clinical stability groups: Group 1 (stability >3 months but <1 year), Group 2 (≥1 year but <2 years) and Group 3 (≥2 years). Melanocyte transplantation was done using suction blister epidermal grafting (SBEG) on a single patch. Blood was drawn for catalase estimation in all patients and 10 healthy controls. A 3-mm punch biopsy was taken on the day of transplantation from the margin of the macule in first 5 patients in each group for immunohistochemistry of CD4, CD8, CD45RO, CD45RA, and FoxP3. Those with ≥ 75% repigmentation at 6 months were labeled as responders. Results:  The success rate was 0% in Group 1, 37.5% in Group 2 and 77.8% in Group 3. The difference in the success rate between the groups was statistically significant (p=0.005). The median period of stability was significantly higher in the responders compared to the non-responders (p=0.001). Catalase levels were not significantly different between patients in the 3 groups, cases and controls, and between responders and non-responders. Lesional CD8 cells were significantly higher in Group 1 compared to Group 3. Percentage of CD8 and CD45RO cells were significantly higher in the non-responders compared to the responders. Conclusion:  Along with clinical stability, proportion of CD8 and CD45RO cells in skin biopsies might help in determining stability of disease and thereby predicting success of transplantation.

A Domino Knoevenagel Hetero-Diels-Alder Reaction for the Synthesis of Polycyclic Chromene Derivatives and Evaluation of Their Cytotoxicity

Bioorganic & Medicinal Chemistry Letters. Mar, 2012  |  Pubmed ID: 22330634

A novel octahydrochromeno[4,3-a]xanthen-1(2H)-one derivatives has been prepared using 10mol% dl-proline in ethanol via a domino Knoevenagel hetero-Diels-Alder reaction of alkene-tethered chromene-3-carboxaldehyde with cyclic 1,3-diketones. This is not only the first example on the preparation of highly diastereoselective pentacyclic chromene derivatives from alkene appended chromene-3-carboxaldehyde in one-pot process at ambient temperature but also preliminary evaluation of the cytotoxic activity of these chromene derivatives. Some of these compounds are found to exhibit potent cytotoxicity against two carcinoma cell lines A549 and B-16.

Role of MMP-2 in the Regulation of IL-6/Stat3 Survival Signaling Via Interaction with α5β1 Integrin in Glioma

Oncogene. Feb, 2012  |  Pubmed ID: 22349830

Matrix metalloproteinase-2 (MMP-2) has pivotal role in the degradation of extracellular matrix, and thereby enhances the invasive, proliferative and metastatic potential in cancer. Knockdown of MMP-2 using MMP-2 small interfering RNA (pM) in human glioma xenograft cell lines 4910 and 5310 decreased cell proliferation compared with mock and pSV (scrambled vector) treatments, as determined by 5-bromo-2'-deoxyuridine incorporation, Ki-67 staining and clonogenic survival assay. Cytokine array and western blotting using tumor-conditioned media displayed modulated secretory levels of various cytokines including granulocyte-macrophage colony-stimulating factor, interleukin-6 (IL-6), IL-8, IL-10, tumor necrosis factor-α, angiogenin, vascular endothelial growth factor and PDGF-BB in MMP-2 knockdown cells. Further, cDNA PCR array indicated potential negative regulation of Janus kinase/Stat3 pathway in pM-treated cells. Mechanistically, MMP-2 is involved in complex formation with α5 and β1 integrins and MMP-2 downregulation inhibited α5β1 integrin-mediated Stat3 phosphorylation and nuclear translocation. Electrophoretic mobility shift assay and chromatin immunoprecipitation assays showed inhibited Stat3 DNA-binding activity and recruitment at CyclinD1 and c-Myc promoters in pM-treated cells. In individual experiments, IL-6 or siRNA-insensitive MMP-2 overexpression by pM-FL-A141G counteracted and restored the pM-inhibited Stat3 DNA-binding activity, suggesting IL-6/Stat3 signaling suppression in pM-treated 4910 and 5310 cells. MMP-2/α5β1 binding is enhanced in human recombinant MMP-2 treatments, resulting in elevated Stat3 DNA-binding activity and recruitment on CyclinD1 and c-Myc promoters. Activation of α5β1 signaling by Fibronectin adhesion elevated pM-inhibited Stat3 phosphorylation whereas blocking α5β1 abrogated constitutive Stat3 activation. In vivo experiments with orthotropic tumor model revealed the decreased tumor size in pM treatment compared with mock or pSV treatments. Immunofluorescence studies in tumor sections corroborated our in vitro findings evidencing high expression and co-localization of MMP-2/α5β1, which is decreased upon pM treatment along with significantly reduced IL-6, phospho-Stat3, CyclinD1, c-Myc, Ki-67 and PCNA expression levels. Our data indicate the possible role of MMP-2/α5β1 interaction in the regulation of α5β1-mediated IL-6/Stat3 signaling activation and signifies the therapeutic potential of blocking MMP-2/α5β1 interaction in glioma treatment.Oncogene advance online publication, 20 February 2012; doi:10.1038/onc.2012.52.

Gamma Secretase Inhibition Promotes Hypoxic Necrosis in Mouse Pancreatic Ductal Adenocarcinoma

The Journal of Experimental Medicine. Feb, 2012  |  Pubmed ID: 22351932

Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease that is refractory to medical intervention. Notch pathway antagonism has been shown to prevent pancreatic preneoplasia progression in mouse models, but potential benefits in the setting of an established PDA tumor have not been established. We demonstrate that the gamma secretase inhibitor MRK003 effectively inhibits intratumoral Notch signaling in the KPC mouse model of advanced PDA. Although MRK003 monotherapy fails to extend the lifespan of KPC mice, the combination of MRK003 with the chemotherapeutic gemcitabine prolongs survival. Combination treatment kills tumor endothelial cells and synergistically promotes widespread hypoxic necrosis. These results indicate that the paucivascular nature of PDA can be exploited as a therapeutic vulnerability, and the dual targeting of the tumor endothelium and neoplastic cells by gamma secretase inhibition constitutes a rationale for clinical translation.

Oral Field Cancerization: Current Evidence and Future Perspectives

Oral and Maxillofacial Surgery. Feb, 2012  |  Pubmed ID: 22354325

INTRODUCTION: Oral field cancerization implies that oral cancer does not arise as an isolated cellular phenomenon but rather as an anaplastic tendency involving many cells at once and results in the multifocal development of cancer at various rates within the entire field in response to a carcinogen especially tobacco. This concept has been frequently used to explain the occurrence of multiple primary cancers and recurrences following complete excision of oral cancer. DISCUSSION: This review deals in detail with the origin, principle, various theories used to explain this effect and molecular, genetic, as well as cytogenetic findings related to oral field cancerization. Further, the clinical implications and future research directives are also discussed.

Enhanced Electron Field Emission Properties of High Aspect Ratio Silicon Nanowire-zinc Oxide Core-shell Arrays

Physical Chemistry Chemical Physics : PCCP. Feb, 2012  |  Pubmed ID: 22354387

The enhanced electron field emission (EFE) properties of high aspect ratio, vertically aligned SiNW-ZnO core-shell arrays are presented. These core-shell arrays are prepared by a thin, controlled, highly crystalline and conformal coating of zinc oxide as shell using the plasma assisted-atomic layer deposition (PA-ALD) route on vertically aligned silicon nanowire arrays core. The core-shell nanostuctures are confirmed by HRTEM imaging along with the individual elemental mapping demonstrating the conformal deposition of 10 nm ZnO on the SiNWs. EFE properties of va-SiNW-ZnO core-shell arrays showed a high emission current density of 51 μA cm(-2) and a low turn on field of 7.6 V μm(-1) (defined at a current density of 1 μA cm(-2)) compared to the 3.2 μA cm(-2) emission current density and 9.1 V μm(-1) turn on field for SiNWs. The field enhancement factor (β) of 4227 for the devices demonstrates that these core-shell nanowire arrays are excellent field-emitters. Such an enhancement in the field emission originates from the details of the band structure of this peculiar material combination resulting in good electron transport from SiNW to ZnO as evident from the band diagram of the core-shell material. This is further supported by the conducting AFM studies where lowering in threshold voltage by 1 eV confirms the role of ZnO coating in the enhancement of the emission characteristics.

Early Surgical Debridement in the Management of Infectious Scleritis After Pterygium Excision

Journal of Ophthalmic Inflammation and Infection. Feb, 2012  |  Pubmed ID: 22354483

PURPOSE: The purpose of this study was to report outcomes of infectious scleritis after pterygium surgery, managed with antibiotic therapies and early scleral debridement. METHODS: Retrospective chart review of 13 consecutive cases of infectious scleritis after pterygium excision between 1999 and 2009 was conducted. Collected data included prior medical and surgical history, latency period between pterygium surgery and presentation of infectious scleritis, culture and histopathologic findings, antibiotic regimen, length of hospital stay, visual acuity before and after treatment, and complications. RESULTS: Median follow-up was at 14 months. Twelve patients underwent prompt surgical debridement after infectious scleritis diagnosis (median, 2.5 days). Debridement was delayed in one patient. Median hospital stay was 3 days. Best-corrected visual acuity improved in ten patients, remained stable in one patient, and decreased in two patients following treatment. Complications included scleral thinning requiring scleral patch graft (1/13), glaucoma (3/13), and progression to phthisis bulbi (1/13). No patients required enucleation. CONCLUSIONS: In contrast to the generally poor outcomes in the literature, early surgical debridement of pterygium-associated infectious scleritis appears to offer improved prognosis.

Effect of an Injury Awareness Education Program on Risk-taking Behaviors and Injuries in Juvenile Justice Offenders: a Retrospective Cohort Study

PloS One. 2012  |  Pubmed ID: 22355394

Risk-taking behavior is a leading cause of injury and death amongst young people.

Hyperprolactinemia With Aripiprazole: Understanding the Paradox

American Journal of Therapeutics. Feb, 2012  |  Pubmed ID: 22357167

Aripiprazole, due to its partial agonist activity at the D2 receptors, is often recommended as the drug of choice in patients who develop antipsychotic-induced hyperprolactinemia. We report a case of a female patient who developed hyperprolactinemia while on treatment with aripiprazole. This partial D2 agonistic activity of aripiprazole could be dose related, and hence, at higher doses, aripiprazole by itself can have dopamine antagonistic properties and hence cause prolactin system abnormalities.

Laser Management of Acne Scarring

Skin Therapy Letter. Feb, 2012  |  Pubmed ID: 22358306

Acne scarring is often challenging to manage. Various laser treatments are helpful in addressing abnormal color and texture in order to improve the appearance of an acne scar. This paper will review the appropriate use and side-effects of these laser treatments.

Irinotecan Loaded in Eluting Beads: Preclinical Assessment in a Rabbit VX2 Liver Tumor Model

Cardiovascular and Interventional Radiology. Feb, 2012  |  Pubmed ID: 22358992

PURPOSE: The purpose of this study was to study the pharmacokinetics of irinotecan injected intravenously, intra-arterially, or loaded onto a delivery platform. MATERIAL AND METHODS: Fifty-four New Zealand White rabbits with VX2 liver tumor, divided in 3 groups of 17 rabbits, each received irinotecan either by intravenous (IV) route, intra-arterial hepatic (IA) route, or loaded on drug-eluting beads (DEBIRI). Animals were killed at 1, 6, and 24 h. Irinotecan and SN-38 concentrations were measured at different time points in serum, tumor, and normal liver. RESULTS: Twelve milligrams of irinotecan were injected IV and IA, whereas 6-16.5 mg were injected loaded onto DEBIRI. Normalized serum irinotecan reached a peak of 333 ng/ml (range 198.8-502.5) for IV, 327.1 ng/ml (range 277.1-495.6) for IA, and 189.7 ng/ml (range 111.1-261.9) for DEBIRI (P < 0.001) delivery. The area-under-the-curve value from 10 to 60 min of serum irinotecan concentration was significantly lower for DEBIRI (P = 0.0009). Tumor irinotecan levels for IV, IA, and DEBIRI (in ng/200 mg of tissue followed by ranges in parentheses) were, respectively, 23.6 (0.3-24.9), 36.5 (7.7-1914.1), and 20.2 (2.9-319) at 1 h; 4.2 (1-27.9), 99.3 (46.6-159.5), and 42.1 (11.3-189) at 6 h; and 2.7 (2.5-6.9), 18.3 (1.5-369.1), and 174.4 (3.4-5147.3) at 24 h (P = 0.02). At 24 h, tumor necrosis was 25% (10-30), 60% (40-91.25), and 95% (76.25-95) for IV, IA, and DEBIRI, respectively (P = 0.03). CONCLUSION: Compared with IV or IA, DEBIRI induces lower early serum levels of irinotecan, a high and prolonged intratumoral level of irinotecan, and a greater rate of tumor necrosis at 24 h. Further evaluation of the clinical benefit of DEBIRI is warranted.

Tissue Factor-positive Monocytes in Children with Sickle Cell Disease: Correlation with Biomarkers of Haemolysis

British Journal of Haematology. Feb, 2012  |  Pubmed ID: 22360627

Tissue Factor (TF) initiates thrombin generation, and whole blood TF (WBTF) is elevated in sickle cell disease (SCD). We sought to identify the presence of TF-positive monocytes in SCD and their relationship with the other coagulation markers including WBTF, microparticle-associated TF, thrombin-antithrombin (TAT) complexes and D-dimer. Whether major SCD-related pathobiological processes, including haemolysis, inflammation and endothelial activation, contribute to the coagulation abnormalities was also studied. The cohort comprised children with SCD (18 HbSS, 12 HbSC, mean age 3·6 years). We demonstrated elevated levels of TF-positive monocytes in HbSS, which correlated with WBTF, TAT and D-dimer (P = 0·02 to P = 0·0003). While TF-positive monocytes, WBTF, TAT and D-dimer correlated with several biomarkers of haemolysis, inflammation and endothelial activation in univariate analyses, in multiple regression models the haemolytic markers (reticulocytes and lactate dehydrogenase) contributed exclusively to the association with all four coagulant markers evaluated. The demonstration that haemolysis is the predominant operative pathology in the associated perturbations of coagulation in HbSS at a young age provides additional evidence for the early use of therapeutic agents, such as hydroxycarbamide to reduce the haemolytic component of this disease.

A Proof-of-Concept Randomized Controlled Study of Gabapentin: Effects on Cannabis Use, Withdrawal and Executive Function Deficits in Cannabis-Dependent Adults

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. Feb, 2012  |  Pubmed ID: 22373942

There are no FDA-approved pharmacotherapies for cannabis dependence. Cannabis is the most widely used illicit drug in the world, and patients seeking treatment for primary cannabis dependence represent 25% of all substance use admissions. We conducted a phase IIa proof-of-concept pilot study to examine the safety and efficacy of a calcium channel/GABA modulating drug, gabapentin, for the treatment of cannabis dependence. A 12-week, randomized, double-blind, placebo-controlled clinical trial was conducted in 50 unpaid treatment-seeking male and female outpatients, aged 18-65 years, diagnosed with current cannabis dependence. Subjects received either gabapentin (1200 mg/day) or matched placebo. Manual-guided, abstinence-oriented individual counseling was provided weekly to all participants. Cannabis use was measured by weekly urine toxicology and by self-report using the Timeline Followback Interview. Cannabis withdrawal symptoms were assessed using the Marijuana Withdrawal Checklist. Executive function was measured using subtests from the Delis-Kaplan Executive Function System. Relative to placebo, gabapentin significantly reduced cannabis use as measured both by urine toxicology (p=0.001) and by the Timeline Followback Interview (p=0.004), and significantly decreased withdrawal symptoms as measured by the Marijuana Withdrawal Checklist (p<0.001). Gabapentin was also associated with significantly greater improvement in overall performance on tests of executive function (p=0.029). This POC pilot study provides preliminary support for the safety and efficacy of gabapentin for treatment of cannabis dependence that merits further study, and provides an alternative conceptual framework for treatment of addiction aimed at restoring homeostasis in brain stress systems that are dysregulated in drug dependence and withdrawal.Neuropsychopharmacology advance online publication, 29 February 2012; doi:10.1038/npp.2012.14.

Preoperative Embolization of Replaced Right Hepatic Artery Prior to Pancreaticoduodenectomy

Journal of Surgical Oncology. Feb, 2012  |  Pubmed ID: 22374866

Aberrancy of the hepatic arterial anatomy is common. Because of its course directly adjacent to the head of the pancreas, a replaced right hepatic artery (RHA) is vulnerable to invasion by peri-pancreatic malignancies. Division of the RHA at the time of pancreaticoduodenectomy, however, may result in hepatic infarction and/or bilioenteric anastomotic complications. We report two cases of patients undergoing preoperative embolization of tumor encased replaced RHAs to allow for sufficient collateralization prior to pancreaticoduodenectomy. J. Surg. Oncol © 2012 Wiley Periodicals, Inc.

Da Vinci® Single-site Platform: Anthropometrical, Docking and Suturing Considerations for Hysterectomy in the Cadaver Model

The International Journal of Medical Robotics + Computer Assisted Surgery : MRCAS. Feb, 2012  |  Pubmed ID: 22374880

BACKGROUND: The paper describes specific technical requirements, limitations, anthropometrical, docking and suturing considerations on the performance of robotic hysterectomy using the da Vinci® Single-Site Platform in the cadaver model METHODS: A data set was collected for each procedure including port placement, docking sequence, robotic arms placement and angles, robotic instrumentation, optimal ergonomics, operative time, and cadaver anthropometrical measurements. Pearson correlation coefficients were calculated to determine whether age, BMI or docking approach were correlated with docking difficulty and likelihood of successful procedure completion. Analysis of the data was performed using SPSS v19.0.0. RESULTS: The planned surgical procedure was successfully completed with single-port robotics in 87.5% of cases. High BMI was correlated with difficulty docking the robot, correlation coefficient 0.98. CONCLUSIONS: Further work is needed in the development and advancement of single-site robotic platforms, articulated instrumentation, and optics. Copyright © 2012 John Wiley & Sons, Ltd.

Pay Attention to Esophageal Mucosa in Achalasia

Indian Journal of Gastroenterology : Official Journal of the Indian Society of Gastroenterology. Feb, 2012  |  Pubmed ID: 22307887

Effects of Disorder on the Optical Properties of CVD Grown Polycrystalline Graphene

Nanoscale. Mar, 2012  |  Pubmed ID: 22307891

We explore the effects of crystallite size (L(a)) on the linear and non-linear optical properties of chemical vapor deposition grown polycrystalline graphene. The π-plasmon resonance present at ∼4.75 eV (∼260 nm) in the optical absorption spectrum of graphene follows the empirical relationship λ(π) = 250.5 nm + 89.5 nm(2)/L(a), where λ(π) represents the π-plasmon wavelength. Furthermore, our Z-scan studies reveal that the crystallite size significantly changes the saturation intensity in CVD grown graphene. Notably, in comparison to epitaxial graphene layers grown on SiC wafers which exhibit a photogenerated carrier lifetime of few picoseconds, we find that the photogenerated carriers in our CVD grown graphene can exhibit lifetimes as long as nanoseconds.

A New Practical Approach Towards the Synthesis of Unsymmetric and Symmetric 1,10-phenanthroline Derivatives at Room Temperature

Chemical Communications (Cambridge, England). Mar, 2012  |  Pubmed ID: 22310647

An efficient method towards synthesis of 1,10-phenanthrolines is described. Through Lewis acid-catalyzed annulation reaction between 3-ethoxycyclobutanones and 8-aminoquinolines, a variety of unsymmetric and symmetric 1,10-phenanthroline derivatives were readily prepared with high regioselectivity at room temperature.

Accuracy of ECG Interpretation in Competitive Athletes: the Impact of Using Standised ECG Criteria

British Journal of Sports Medicine. Feb, 2012  |  Pubmed ID: 22310648

BackgroundInterpretation of ECGs in athletes is complicated by physiological changes related to training. The purpose of this study was to determine the accuracy of ECG interpretation in athletes among different physician specialties, with and without use of a standised ECG criteria tool.MethodsPhysicians were asked to interpret 40 ECGs (28 normal ECGs from college athletes randomised with 12 abnormal ECGs from individuals with known ciovascular pathology) and classify each ECG as (1) 'normal or variant - no further evaluation and testing needed' or (2) 'abnormal - further evaluation and testing needed.' After reading the ECGs, participants received a two-page ECG criteria tool to guide interpretation of the ECGs again.ResultsA total of 60 physicians participated: 22 primary care (PC) residents, 16 PC attending physicians, 12 sports medicine (SM) physicians and 10 ciologists. At baseline, the total number of ECGs correctly interpreted was PC residents 73%, PC attendings 73%, SM physicians 78% and ciologists 85%. With use of the ECG criteria tool, all physician groups significantly improved their accuracy (p<0.0001): PC residents 92%, PC attendings 90%, SM physicians 91% and ciologists 96%. With use of the ECG criteria tool, specificity improved from 70% to 91%, sensitivity improved from 89% to 94% and there was no difference comparing ciologists versus all other physicians (p=0.053).ConclusionsProviding standised criteria to assist ECG interpretation in athletes significantly improves the ability to accurately distinguish normal from abnormal findings across physician specialties, even in physicians with little or no experience.

Isolation and Characterisation of an HpSHP Gene from Hosta Plantaginea

Molecular Biology Reports. Feb, 2012  |  Pubmed ID: 22311025

Based on genetic and molecular analyses, the ABC model has been proposed to explain the genetic control of floral development. C-class MADS-box genes play crucial roles in Arabidopsis thaliana development by regulating the organ identities of stamens and gynoecium. The present research reports for the first time the cloning of an HpSHP gene from Hosta plantaginea (Lam.) Aschers. Phylogenetic analysis shows that HpSHP is a member of the C-class MADS-box genes that is closely related to C-lineage SHP homologues from monocot species. Semi-quantitative and real-time polymerase chain reaction analyses show that HpSHP expression is stamen and gynoecium specific. HpSHP also has spatial and temporal expression patterns in the reproductive organs of H. plantaginea. A functional analysis is carried out in Arabidopsis by overexpression of HpSHP. Homeotic transformations of sepals into carpelloid organs, bent ovaries, and prematurely shattering fruits are observed in 35S::HpSHP transgenic plants. All these results show that HpSHP plays a crucial role in gynoecium development.

Neuroinflammation and Synaptic Loss

Neurochemical Research. Feb, 2012  |  Pubmed ID: 22311128

Neuroinflammation plays a critical role in the progression of many neurodegenerative, neuropsychiatric and viral diseases. In neuroinflammation, activated microglia and astrocytes release cytokines and chemokines as well as nitric oxide, which in turn activate many signal transduction pathways. The cytokines, interleukin-1 beta and tumor necrosis factor alpha, regulate transcription of a number of genes within the brain, which can lead to the formation of pro-inflammatory products of the arachidonic acid cascade. Formation of pro-inflammatory agents and associated cytotoxic products during neuroinflammation can be detrimental to neurons by altering synaptic proteins. Neuroinflammation as well as excitotoxic insults reduce synaptic markers such as synaptophysin and drebrin. Neurodegenerative, neuropsychiatric illnesses and viral infections are accompanied by loss of both pre- and post-synaptic proteins. These synaptic changes may contribute to the progressive cognitive decline and behavioral changes associated with these illnesses.

Influence of Surgical Technique on Mastectomy and Reexcision Rates in Breast-conserving Therapy for Cancer

International Journal of Surgical Oncology. 2012  |  Pubmed ID: 22312542

Introduction. Breast conserving surgery (BCS) requires tumor excision with negative margins. Reexcision rates of 30-50% are reported. Ultrasound localization, intraoperative margin pathology, and specimen mammography have reduced reexcisions, but require new equipment. Cavity shave margin (CSM) is a technique, utilizing existing equipment, that potentially reduces reexcision. This study evaluates CSM reexcision impact. Methods. 522 cancers treated with BCS were reviewed. Patients underwent standard partial mastectomy (SPM) or CSM. Data collected included demographics, pathology, and treatments. Results. 455 SPMs were compared to 67 CSMs. Analysis revealed no differences in pathology, intraductal component, or neoadjuvant chemotherapy. Overall reexcision rate = 43%. Most reexcisions were performed for DCIS at margin. SPMs underwent 213 reexcisions (46.8%), versus 16/67 (23.9%) CSMs (P = 0.0003). Total mastectomy as definitive procedure was performed after more SPMs (P = 0.009). Multivariate analysis revealed CSM, % DCIS, tumor size, and race to influence reexcisions. Conclusions. CSM is a technique that reduces reexcisions and mastectomy rates.

RNT4 3'-UTR Insertion/Deletion Polymorphisms Are Not Associated with Atrial Septal Defect in Chinese Han Population: A Brief Communication

DNA and Cell Biology. Feb, 2012  |  Pubmed ID: 22313113

Atrial septal defect (ASD) is a common type of congenital heart disease, which is defined as any communication through atrial septum. Several studies have revealed that genetic factors may influence the susceptibility of ASD. Recent studies have shown that reticulon 4 (RTN4) gene might be involved in some processes relevant to heart development, such as regulation of cell migration and vascular remodeling. This study aimed to evaluate RTN4 gene polymorphisms of CAA and TATC insertion/deletion in relation to the risk of ASD in Chinese Han population. A total of 175 ASD patients and 308 unrelated healthy controls were successfully investigated. The polymorphisms of patients were determined by polymerase chain reaction-polyacrylamide gel electrophoresis. There was no significant difference in the allele frequencies of CAA and TATC insertion/deletion in RNT4 gene between ASD patients and controls. The same results were seen in their genotypes. The present study suggests that CAA and TATC insertion/deletion polymorphisms of RNT4 gene may not be a useful marker to predict the susceptibility of ASD in Chinese Han population.

The Neuropeptide Neuromedin U Promotes Autoantibody-mediated Arthritis

Arthritis Research & Therapy. Feb, 2012  |  Pubmed ID: 22314006

ABSTRACT: INTRODUCTION: Neuromedin U (NMU) is a neuropeptide with pro-inflammatory activity. The primary objective of this study was to determine if NMU promotes autoantibody-induced arthritis. Additional studies addressed the cellular source of NMU and sought to define the NMU receptor responsible for its pro-inflammatory effects. METHODS: Serum containing arthritogenic autoantibodies from K/BxN mice was used to induce arthritis in mice genetically lacking NMU. Parallel experiments examined whether NMU deficiency impacted the early mast-cell-dependent vascular leak response induced by these autoantibodies. Bone-marrow chimeric mice were generated to determine whether pro-inflammatory NMU is derived from hematopoietic cells or stromal cells. Mice lacking the known NMU receptors singly and in combination were used to determine susceptibility to serum-transferred arthritis and in vitro cellular responses to NMU. RESULTS: NMU-deficient mice developed less severe arthritis than control mice. Vascular leak was not affected by NMU deficiency. NMU expression by bone-marrow-derived cells mediated the pro-arthritogenic effect. Deficiency of all of the known NMU receptors, however, had no impact on arthritis severity and did not affect the ability of NMU to stimulate intracellular calcium flux. CONCLUSIONS: NMU-deficient mice are protected from developing autoantibody-induced inflammatory arthritis. NMU derived from hematopoietic cells, not neurons, promotes the development of autoantibody-induced inflammatory arthritis. This effect is mediated by a receptor other than the currently known NMU receptors.

A Joint Effect of New Western Diet and Retinoid X Receptor Alpha Prostate-specific Knockout with Development of High-grade Prostatic Intraepithelial Neoplasia in Mice-A Preliminary Study

The Prostate. Feb, 2012  |  Pubmed ID: 22314496

BACKGROUND: The "New Western-style Diet" (NWD) characterized by high in fat and low in fiber, vitamin D, calcium, and methyl donors-are considered as a risk factor for prostate cancer. Previous studies have shown that premalignant lesions of human prostate have decreased expression of the Retinoid X Receptor alpha (RXRα). This study was to determine the effect of diet in RXRα knockout mice in developing high-grade prostate intraepithelial neoplasia (mPIN). METHODS: Male mice (n = 54) with or without the RXRα prostate null mutation were fed either NWD or AIN-76A control diet for 10 months; prostates were harvested at 11 months of age and examined for prostate mPIN. RESULTS: mPIN was seen in 79% of RXRα prostate null mice fed NWD (n = 19), 30.8% RXRα prostate null mice fed AIN-76A (n = 13), 42.9% RXRα wild-type mice fed NWD (n = 14), and 12.5% RXRα wild-type mice fed AIN-76A (n = 8). Unconditional Logistic analysis showed a significant joint effect of NWD and RXRα status in developing mPIN 26.3 (95% CI: 2.5-280), but interaction was not significant owing to the small sample size 1.6 (0.09-27.7, P = 0.7441). CONCLUSION: This study provides preliminary data to support a joint RXRα-diet effect in prostate carcinogenesis. Prostate © 2012 Wiley Periodicals, Inc.

Ab Initio and Density Functional Theoretical Design and Screening of Model Crown Ether Based Ligand (host) for Extraction of Lithium Metal Ion (guest): Effect of Donor and Electronic Induction

Journal of Molecular Modeling. Feb, 2012  |  Pubmed ID: 22318713

The structures, energetic and thermodynamic parameters of model crown ethers with different donor, cavity and electron donating/ withdrawing functional group have been determined with ab initio MP2 and density functional theory in gas and solvent phase. The calculated values of binding energy/ enthalpy for lithium ion complexation are marginally higher for hard donor based aza and oxa crown compared to soft donor based thia and phospha crown. The calculated values of binding enthalpy for lithium metal ion with 12C4 at MP2 level of theory is in good agreement with the available experimental result. The binding energy is altered due to the inductive effect imparted by the electron donating/ withdrawing group in crown ether, which is well correlated with the values of electron transfer. The role of entropy for extraction of hydrated lithium metal ion by different donor and functional group based ligand has been demonstrated. The HOMO-LUMO gap is decreased and dipole moment of the ligand is increased from gas phase to organic phase because of the dielectric constant of the solvent. The gas phase binding energy is reduced in solvent phase as the solvent molecules weaken the metal-ligand binding. The theoretical values of extraction energy for LiCl salt from aqueous solution in different organic solvent is validated by the experimental trend. The study presented here should contribute to the design of model host ligand and screening of solvent for metal ion recognition and thus can contribute in planning the experiments.

Ferromagnetism in Graphene Nanoribbons: Split Versus Oxidative Unzipped Ribbons

Nano Letters. Feb, 2012  |  Pubmed ID: 22320177

Two types of graphene nanoribbons: (a) potassium-split graphene nanoribbons (GNRs), and (b) oxidative unzipped and chemically converted graphene nanoribbons (CCGNRs) were investigated for their magnetic properties using the combination of static magnetization and electron spin resonance measurements. The two types of ribbons possess remarkably different magnetic properties. While a low-temperature ferromagnet-like feature is observed in both types of ribbons, such room-temperature feature persists only in potassium-split ribbons. The GNRs show negative exchange bias, but the CCGNRs exhibit a "positive exchange bias". Electron spin resonance measurements suggest that the carbon-related defects may be responsible for the observed magnetic behavior in both types of ribbons. Furthermore, information on the proton hyperfine coupling strength has been obtained from hyperfine sublevel correlation experiments performed on the GNRs. Electron spin resonance finds no evidence for the presence of potassium (cluster) related signals, pointing to the intrinsic magnetic nature of the ribbons. Our combined experimental results may indicate the coexistence of ferromagnetic clusters with antiferromagnetic regions leading to disordered magnetic phase. We discuss the possible origin of the observed contrast in the magnetic behaviors of the two types of ribbons studied.

Genetic Variation in RTN4 3'-UTR and Susceptibility to Cervical Squamous Cell Carcinoma

DNA and Cell Biology. Feb, 2012  |  Pubmed ID: 22320844

Recent studies have suggested that RTN4 is a multifunctional gene, including inhibition of axonal regeneration, vascular remodeling, apoptosis, and tumor suppression. The TATC and CAA insertion/deletion polymorphisms of RTN4 3'-UTR have been linked to schizophrenia, depression, and dilated cardiomyopathy. To test whether these two polymorphisms are associated with cervical squamous cell carcinoma (CSCC), in this research, by using polymerase chain reaction-polyacrylamide gel electrophoresis, we determined the genotypes of the TATC and CAA polymorphisms in 336 CSCC patients and 450 unrelated control subjects. Allele frequencies of TATC and CAA polymorphisms were not significantly different between CSCC patients and control subjects (odds ratio [OR]=1.22, 95% confidence interval [CI]=0.98-1.50 for TATC; OR=0.95, 95% CI=0.76-1.18 for CAA). Decreased CSCC risk was associated with TATC polymorphism in a recessive model (OR=0.49, 95% CI=0.30-0.77), while no significant association was observed between CAA polymorphism and CSCC in different genetic models. Results of stratified analysis revealed that both TATC and CAA polymorphisms were associated with high clinical stage, and CAA polymorphism was also associated with positive parametrial invasion (OR=0.69, 95% CI=0.48-0.98). The present study provides evidence that TATC and CAA insertion/deletion polymorphisms are associated with CSCC, indicating that genetic variation in RTN4 3'-UTR contributes to the susceptibility to CSCC. It is necessary to confirm these findings in ethnically different populations and with a larger sample.

Novel Microbial Route to Synthesize ZnO Nanoparticles Using Aeromonas Hydrophila and Their Activity Against Pathogenic Bacteria and Fungi

Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy. Jan, 2012  |  Pubmed ID: 22321514

In the present work, we describe a low-cost, unreported and simple procedure for biosynthesis of zinc oxide nanoparticles (ZnO NPs) using reproducible bacteria, Aeromonas hydrophila as eco-friendly reducing and capping agent. UV-vis spectroscopy, XRD, FTIR, AFM, NC-AFM and FESEM with EDX analyses were performed to ascertain the formation and characterization of ZnO NPs. The synthesized ZnO NPs were characterized by a peak at 374nm in the UV-vis spectrum. XRD confirmed the crystalline nature of the nanoparticles and AFM showed the morphology of the nanoparticle to be spherical, oval with an average size of 57.72nm. Synthesized ZnO NPs showed the XRD peaks at 31.75°, 34.37°, 47.60°, 56.52°, 66.02° and 75.16° were identified as (100), (002), (101), (102), (110), (112) and (202) reflections, respectively. Rietveld analysis to the X-ray data indicated that ZnO NPs have hexagonal unit cell at crystalline level. The size and topological structure of the ZnO NPs was measured by NC-AFM. The morphological characterization of synthesized nanoparticles was analyzed by FESEM and chemical composition by EDX. The antibacterial and antifungal activity was ended with corresponding well diffusion and minimum inhibitory concentration. The maximum zone of inhibition was observed in the ZnO NPs (25μg/mL) against Pseudomonas aeruginosa (22±1.8mm) and Aspergillus flavus (19±1.0mm). Bacteria-mediated ZnO NPs were synthesized and proved to be a good novel antimicrobial material for the first time in this study.

Effects of Doxycycline on Gene Expression in Wolbachia and Brugia Malayi Adult Female Worms in Vivo

Journal of Biomedical Science. Feb, 2012  |  Pubmed ID: 22321609

ABSTRACT: BACKGROUND: Most filarial nematodes contain Wolbachia symbionts. The purpose of this study was to examine the effects of doxycycline on gene expression in Wolbachia and adult female Brugia malayi. METHODS: Brugia malayi infected gerbils were treated with doxycycline for 6-weeks. This treatment largely cleared Wolbachia and arrested worm reproduction. RNA recovered from treated and control female worms was labeled by random priming and hybridized to the Version 2- filarial microarray to obtain expression profiles. RESULTS AND DISCUSSION: Results showed significant changes in expression for 200 Wolbachia (29% of Wolbachia genes with expression signals in untreated worms) and 546 B. malayi array elements after treatment. These elements correspond to known genes and also to novel genes with unknown biological functions. Most differentially expressed Wolbachia genes were down-regulated after treatment (98.5%). In contrast, doxycycline had a mixed effect on B. malayi gene expression with many more genes being significantly up-regulated after treatment (85% of differentially expressed genes). Genes and processes involved in reproduction (gender-regulated genes, collagen, amino acid metabolism, ribosomal processes, and cytoskeleton) were down-regulated after doxycycline while up-regulated genes and pathways suggest adaptations for survival in response to stress (energy metabolism, electron transport, anti-oxidants, nutrient transport, bacterial signaling pathways, and immune evasion). CONCLUSIONS: Doxycycline reduced Wolbachia and significantly decreased bacterial gene expression. Wolbachia ribosomes are believed to be the primary biological target for doxycycline in filarial worms. B. malayi genes essential for reproduction, growth and development were also down-regulated; these changes are consistent with doxycycline effects on embryo development and reproduction. On the other hand, many B. malayi genes involved in energy production, electron-transport, metabolism, anti-oxidants, and others with unknown functions had increased expression signals after doxycycline treatment. These results suggest that female worms are able to compensate in part for the loss of Wolbachia so that they can survive, albeit without reproductive capacity. This study of doxycycline induced changes in gene expression has provided new clues regarding the symbiotic relationship between Wolbachia and B. malayi.

Psychometric Validation of a Knowledge Questionnaire on Micronutrients Among Adolescents and Its Relationship to Micronutrient Status of 15-19-year-old Adolescent Boys, Hyderabad, India

Public Health Nutrition. Feb, 2012  |  Pubmed ID: 22321774

OBJECTIVE: To develop a psychometrically valid questionnaire for testing knowledge on micronutrients and to assess the relationship between knowledge and biomarkers of micronutrient status among adolescents. DESIGN: Cross-sectional, institution-based, validity and reliability study. SETTING: Seven higher secondary schools were covered in the limits of Greater Hyderabad Municipal Corporation, Hyderabad, India. SUBJECTS: Students aged 15-19 years, n 92 for the pre-test, n 108 for test-retest and n 109 for studying the relationship between knowledge and biomarkers of Fe, retinol, ascorbic acid, α-tocopherol, folic acid and vitamin B12 status. RESULTS: From an item pool of 106, thirty-one items were selected based on content validity. Statistical tools to obtain a valid and reliable questionnaire among adolescent boys and girls resulted in eighteen items with a difficulty index of 0·11-0·86, discrimination index of 0·20-0·72 and validity index (point bi-serial correlation) of 0·10-0·62. Reliability as measured by Cronbach's α was 0·71 and the intra-class correlation coefficient was 0·80. A Bland-Altman plot showed good agreement between test and retest scores. The mean response score to the eighteen-item questionnaire was 5·2 (sd 2·68). The mean values of serum retinol were significantly different (P = 0·022) between groups below (24·8 (sd 6·64) μg/dl) and above (28·0 (sd 7·67) μg/dl) the 50th percentile of knowledge score. The relationship persisted after controlling for economic status as a covariate using analysis of covariance (P = 0·018). Other micronutrients did not show any significant relationship. CONCLUSIONS: A valid and reliable eighteen-item knowledge questionnaire was constructed and found to have a significant positive relationship with plasma retinol status alone.

Characteristics and Long-term Outcomes of Percutaneous Revascularization of Unprotected Left Main Coronary Artery Stenosis in the United States a Report from the National Cardiovascular Data Registry, 2004 to 2008

Journal of the American College of Cardiology. Feb, 2012  |  Pubmed ID: 22322080

This study sought to assess percutaneous coronary intervention (PCI) for unprotected left main coronary artery (ULMCA) stenosis in routine U.S. clinical practice.

Survey Shows That at Least Some Physicians Are Not Always Open or Honest with Patients

Health Affairs (Project Hope). Feb, 2012  |  Pubmed ID: 22323169

The Charter on Medical Professionalism, endorsed by more than 100 professional groups worldwide and the US Accreditation Council for Graduate Medical Education, requires openness and honesty in physicians' communication with patients. We present data from a 2009 survey of 1,891 practicing physicians nationwide assessing how widely physicians endorse and follow these principles in communicating with patients. The vast majority of physicians completely agreed that physicians should fully inform patients about the risks and benefits of interventions and should never disclose confidential information to unauthorized persons. Overall, approximately one-third of physicians did not completely agree with disclosing serious medical errors to patients, almost one-fifth did not completely agree that physicians should never tell a patient something untrue, and nearly two-fifths did not completely agree that they should disclose their financial relationships with drug and device companies to patients. Just over one-tenth said they had told patients something untrue in the previous year. Our findings raise concerns that some patients might not receive complete and accurate information from their physicians, and doubts about whether patient-centered care is broadly possible without more widespread physician endorsement of the core communication principles of openness and honesty with patients.

Real-time Monitoring of Shake Flask Fermentation and off Gas Using Triple Disposable Noninvasive Optical Sensors

Biotechnology Progress. Feb, 2012  |  Pubmed ID: 22323391

Bioprocess development is a data-driven process requiring a large number of experiments to be conducted under varying conditions. Small-scale upstream bioprocess development is often performed in shake flasks because they are inexpensive and can be operated in parallel. However, shake flasks are often not equipped to accurately monitor critical process parameters such as pH, dissolved oxygen, and CO(2) concentrations. Therefore, there is no definitive information on oxygen supply of growing cells, CO(2) formation, and pH changes. Here we describe several shake flask fermentations where all three parameters are monitored by disposable noninvasive optical sensors. The sensitive element of these sensors is a thin, luminescent patch affixed inside the flask. Small electronic devices for excitation and fluorescence detection are positioned outside the shake flask for noninvasive monitoring. By measuring the process parameters throughout the course of the E. coli fermentations, we obtain information that is not routinely available in shake flask fermentations. For example, for cultures with only a few millimeters liquid depth, oxygen limitation can occur at relatively low agitation speeds. Under certain conditions oscillations in dissolved oxygen can occur. An increase in shaker speed and a decrease in culture volume can increase the oxygen availability and reduce the duration of oxygen limitation. © 2012 American Institute of Chemical Engineers Biotechnol. Prog.,, 2012.

Pharmacological Blockade of the Cold Receptor TRPM8 Attenuates Autonomic and Behavioral Cold Defenses and Decreases Deep Body Temperature

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Feb, 2012  |  Pubmed ID: 22323721

We studied N-(2-aminoethyl)-N-(4-(benzyloxy)-3-methoxybenzyl)thiophene-2-carboxamide hydrochloride (M8-B), a selective and potent antagonist of the transient receptor potential melastatin-8 (TRPM8) channel. In vitro, M8-B blocked cold-induced and TRPM8-agonist-induced activation of rat, human, and murine TRPM8 channels, including those on primary sensory neurons. In vivo, M8-B decreased deep body temperature (T(b)) in Trpm8(+/+) mice and rats, but not in Trpm8(-/-) mice, thus suggesting an on-target action. Intravenous administration of M8-B was more effective in decreasing T(b) in rats than intrathecal or intracerebroventricular administration, indicating a peripheral action. M8-B attenuated cold-induced c-Fos expression in the lateral parabrachial nucleus, thus indicating a site of action within the cutaneous cooling neural pathway to thermoeffectors, presumably on sensory neurons. A low intravenous dose of M8-B did not affect T(b) at either a constantly high or a constantly low ambient temperature (T(a)), but the same dose readily decreased T(b) if rats were kept at a high T(a) during the M8-B infusion and transferred to a low T(a) immediately thereafter. These data suggest that both a successful delivery of M8-B to the skin (high cutaneous perfusion) and the activation of cutaneous TRPM8 channels (by cold) are required for the hypothermic action of M8-B. At tail-skin temperatures <23°C, the magnitude of the M8-B-induced decrease in T(b) was inversely related to skin temperature, thus suggesting that M8-B blocks thermal (cold) activation of TRPM8. M8-B affected all thermoeffectors studied (thermopreferendum, tail-skin vasoconstriction, and brown fat thermogenesis), thus suggesting that TRPM8 is a universal cold receptor in the thermoregulation system.

Weak and Nondiscriminative Responses to Conspecifics in the Rat Hippocampus

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Feb, 2012  |  Pubmed ID: 22323725

Little is known about how hippocampal neurons in rodents respond to and represent conspecifics. To address this question, we let rats interact while quantifying hippocampal neuronal activation patterns with extracellular recordings and immediate-early gene (c-Fos) expression. A total of 319 single putative pyramidal neurons was recorded in dorsal hippocampus. In sessions with multiple stimulus rats, no cell responded differentially to individual rats (N = 267 cells). We did find, however, that the presence of other rats induced a significant enhancement or suppression of firing in a fraction of neurons (n = 22 of 319; 7%). As expected, a large fraction of neurons (n = 170; 53%) had place fields. There was no evidence for place-independent responses to rats. Rather, the modulations were linked to the spatial responses. While neurons did not discriminate between individual rats, they did discriminate between rats and inanimate objects. Surprisingly, neuronal responses were more strongly modulated by objects than by rats, even though subjects spent more time near their conspecifics. Consistent with the low fraction of rat-modulated cells, social encounters did not induce c-Fos expression in the hippocampus, while there was a social interaction-specific expression in the basolateral amygdala. In both interacting and non-interacting rats, the fraction of c-Fos-expressing cells in the hippocampus was very low. Our investigation of social coding in the rat hippocampus, along with other recent work, showed that social responses were rare and lacked individual specificity, altogether speaking against a role of rodent dorsal hippocampus in social memory.

Identification, Characterization and Quantification of a New Impurity in Deferasirox Active Pharmaceutical Ingredient by LC-ESI-QT/MS/MS

Journal of Pharmaceutical and Biomedical Analysis. Jan, 2012  |  Pubmed ID: 22361658

An unknown impurity was detected in deferasirox drug substance by a newly developed high performance liquid chromatography (HPLC) method. The unknown impurity was identified by liquid chromatography-tandem mass spectrometry using electrospray ionization source and Q-trap mass analyzer (LC-ESI-QT/MS/MS). Based on LC-MS/MS data and knowledge of the synthetic scheme of deferasirox, this impurity was proposed as the regio-isomer of deferasirox. Structural confirmation of this impurity was unambiguously carried out by synthesis followed by characterization using nuclear magnetic resonance (NMR), infrared spectroscopy (IR), mass spectrometry, elemental analysis (EA) and the impurity was confirmed as 2-[3,5-bis(2-hydroxy-phenyl)-[1,2,4]-triazol-1-yl]-benzoic acid (Imp-1). The newly developed method was validated according to ICH guidelines. The resolution between Imp-1 and deferasirox was found to be more than 6.0 and the detection limit of impurities was in the range of 0.0005-0.01%, indicating high selectivity and sensitivity of the newly developed method.

Hepatoblastoma-An Attempt of Histological Subtyping on Fine-needle Aspiration Material

Diagnostic Cytopathology. Feb, 2012  |  Pubmed ID: 22362636

Hepatoblastoma (HB) is classified into epithelial, mixed (epithelial/mesenchymal), and small-cell (anaplastic) type. Wnt/β-catenin pathway plays a key role in hepatic development, regeneration, and tumorigenesis, and HB is known to present β-catenin mutations (50-90%). The present study was undertaken to delineate the cytomorphologic features of HB and to evaluate the feasibility of subtyping of HB on fine-needle aspiration cytology (FNAC). The expression of β-catenin in these tumors was also evaluated both of histopathologic sections and on the aspirated material. Thirty-three cases with fine-needle aspirates of HB were retrieved over a period of 12 years. Cytologic diagnosis was reviewed in the light of clinicoradiological data, response to therapy, and subsequent histopathology. Immunochemistry for β-catenin was performed in 19 of 33 cases on histopathologic sections (n = 10)/cell blocks (n = 6)/cytosmears (n = 3). Based on the cytologic features, the cases were divided into fetal HB (n = 17), embryonal HB (n = 4), combined epithelial HB (n = 8), and mixed HB (n = 4). Four cases of histopathologically proven mixed HB were reported as pure epithelial HB on FNAC, as mesenchymal elements were not represented in the cytology smears. Cytoplasmic as well as nuclear staining for β-catenin was noted in a total of 10 of 19 cases. FNAC can accurately categorize epithelial HB; however, in mixed type, the accuracy depends on number of areas sampled. Cell block can be of help to perform ancillary investigations especially β-catenin for both diagnostic and therapeutic purposes. Cytopathol. 2012; © 2012 Wiley Periodicals, Inc.

The Role of Driving Energy and Delocalized States for Charge Separation in Organic Semiconductors

Science (New York, N.Y.). Feb, 2012  |  Pubmed ID: 22362882

The electron-hole pair created via photon absorption in organic photoconversion systems must overcome the Coulomb attraction to achieve long-range charge separation. We show that this process is facilitated through the formation of excited, delocalized band states. In our experiments on organic photovoltaic cells, these states were accessed for a short time(<1 ps) via IR optical excitation of electron-hole pairs bound at the heterojunction. Atomistic modelling showed that the IR photons promote bound charge pairs to delocalized band states, similar to those formed just after singlet exciton dissociation, which indicates that such states act as the gateway for charge separation. Our results suggest that charge separation in efficient organic photoconversion systems occurs through hot-state charge delocalization rather than energy-gradient-driven intermolecular hopping.

TSC1/2 Signaling Complex Is Essential for Peripheral Naïve CD8 T Cell Survival and Homeostasis in Mice

PloS One. 2012  |  Pubmed ID: 22363451

The PI3K-Akt-mTOR pathway plays crucial roles in regulating both innate and adaptive immunity. However, the role of TSC1, a critical negative regulator of mTOR, in peripheral T cell homeostasis remains elusive. With T cell-specific Tsc1 conditional knockout (Tsc1 KO) mice, we found that peripheral naïve CD8(+) T cells but not CD4(+) T cells were severely reduced. Tsc1 KO naïve CD8(+) T cells showed profound survival defect in an adoptive transfer model and in culture with either stimulation of IL-7 or IL-15, despite comparable CD122 and CD127 expression between control and KO CD8(+) T cells. IL-7 stimulated phosphorylation of Akt(S473) was diminished in Tsc1 KO naïve CD8(+)T cells due to hyperactive mTOR-mediated feedback suppression on PI3K-AKT signaling. Furthermore, impaired Foxo1/Foxo3a phosphorylation and increased pro-apoptotic Bim expression in Tsc1 KO naïve CD8(+)T cells were observed upon stimulation of IL-7. Collectively, our study suggests that TSC1 plays an essential role in regulating peripheral naïve CD8(+) T cell homeostasis, possible via an mTOR-Akt-FoxO-Bim signaling pathway.

Intermittent Hypoxia Regulates Stem-like Characteristics and Differentiation of Neuroblastoma Cells

PloS One. 2012  |  Pubmed ID: 22363512

Neuroblastomas are the most common extracranial solid tumors in children. Neuroblastomas are derived from immature cells of the sympathetic nervous system and are characterized by clinical and biological heterogeneity. Hypoxia has been linked to tumor progression and increased malignancy. Intermittent hypoxia or repeated episodes of hypoxia followed by re-oxygenation is a common phenomenon in solid tumors including neuroblastoma and it has a significant influence on the outcome of therapies. The present study focuses on how intermittent hypoxia modulates the stem-like properties and differentiation in neuroblastoma cells.

Successful Treatment of Calcific Uremic Arteriolopathy with Sodium Thiosulfate in a Renal Transplant Recipient

Renal Failure. Feb, 2012  |  Pubmed ID: 22364415

Calcific uremic arteriolopathy (CUA) is a rare but life-threatening disorder of arteriolar calcification. It frequently leads to severe ischemia, intense pain, and tissue necrosis with non-healing skin ulcerations. CUA usually occurs in patients with chronic kidney disease (CKD), especially those on dialysis, and its occurrence is rare in kidney transplant recipients. The treatment of this disorder is not clearly defined, and no randomized prospective trials are available. Treatment has focused on optimizing dialysis treatment, control of bone mineral parameters, wound care, experimental anticalcification therapies-using bisphosphonates, cinacalcet, parathyroidectomy, and hyperbaric oxygen. Such treatments are based on the pathophysiological considerations and evidences from case reports or series. Recently, several cases have reported about the emerging benefits of intravenous sodium thiosulfate (STS) in the treatment of CUA. STS has resulted in rapid pain relief, wound healing, and prevention of death. We report a case of CUA in a 63-year-old Caucasian man with a functioning renal allograft. In this patient, intravenous STS was administered for 8 months, which was the principal therapy, which resulted in complete resolution of the CUA and skin healing.

Clinical and Economic Outcomes Associated with National Kidney Foundation Guideline-concordant Oral Antidiabetic Drug Treatment Among Type 2 Diabetes Patients with Chronic Kidney Disease

Current Medical Research and Opinion. Feb, 2012  |  Pubmed ID: 22364567

Abstract Objective: To assess outcomes associated with oral anti-diabetic drug (OAD) treatment concordant with guidelines from the National Kidney Foundation (NKF) among type 2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD). Methods: Electronic health record data between 1/1/2005 and 10/31/2010 provided by an integrated health system were analyzed. T2DM patients were selected based on diagnosis from the health record. Patients with stages 3-5 CKD based on diagnosis or lab results were further identified with the date of first indicated CKD set as index date. Patients who had a medication order of OADs within three months of the index date were included. Patients were considered non-guideline-concordant if prescribed OADs that were recommended to be avoided or if they required dosage adjustment, but were unadjusted. Glycemic control, hospital admissions, and costs of encounters were assessed over a 12-month post-index period, and hypoglycemic events were evaluated until loss of follow-up. Regression analyses were performed, adjusting for patient demographic and clinical characteristics. Results: Among 6058 patients (mean age: 70; 42% male), 45% were guideline-concordant. After adjusting for patient characteristics, guideline-concordant patients had a lower risk for hypoglycemic events (HR: 0.72; 95% CI: 0.62-0.83), were less likely to have a hospital admission (OR: 0.87; 95% CI: 0.77-0.98), and more likely to have glycemic control (OR: 1.64, 95% CI: 1.46-1.84). Non-guideline-concordant patients had annual encounter costs of 1.10 times those of guideline-concordant patients (marginal cost = $731; P = 0.04). Limitations: Unobservable confounders may still exist and bias the results; therefore, findings should be interpreted as associations instead of causations. Findings were based on a single integrated health system and may not be generalizable to larger populations. Conclusion: The findings of this exploratory study suggest that guideline-concordant treatment may yield better clinical and economic outcomes. Future research with a better controlled design is warranted to confirm these preliminary findings.

Effect of a CCR1 Receptor Antagonist on Systemic Trafficking of MSCs and Polyethylene Particle-associated Bone Loss

Biomaterials. Feb, 2012  |  Pubmed ID: 22364730

Particle-associated periprosthetic osteolysis remains a major issue in joint replacement. Ongoing bone loss resulting from wear particle-induced inflammation is accompanied by continued attempts at bone repair. Previously we showed that mesenchymal stem cells (MSCs) are recruited systemically to bone exposed to continuous infusion of ultra high molecular weight polyethylene (UHMWPE) particles. The chemokine-receptor axis that mediates this process is unknown. We tested two hypotheses: (1) the CCR1 receptor mediates the systemic recruitment of MSCs to UHMWPE particles and (2) recruited MSCs are able to differentiate into functional mature osteoblasts and decrease particle-associated bone loss. Nude mice were allocated randomly to four groups. UHMWPE particles were continuously infused into the femoral shaft using a micro-pump. Genetically modified murine wild type reporter MSCs were injected systemically via the left ventricle. Non-invasive imaging was used to assay MSC migration and bone mineral density. Bioluminescence and immunohistochemistry confirmed the chemotaxis of reporter cells and their differentiation into mature osteoblasts in the presence of infused particles. Injection of a CCR1 antagonist decreased reporter cell recruitment to the UHMWPE particle infusion site and increased osteolysis. CCR1 appears to be a critical receptor for chemotaxis of MSCs in the presence of UHMWPE particles. Interference with CCR1 exacerbates particle-induced bone loss.

Chromogenic Platform Based on Recombinant Drosophila Melanogaster Acetylcholinesterase for Visible Unidirectional Assay of Organophosphate and Carbamate Insecticide Residues

Analytica Chimica Acta. Mar, 2012  |  Pubmed ID: 22365130

In this study we propose a chromogenic platform for rapid analysis of organophosphate (OP) and carbamate (CM) insecticide residues, based on recombinant Drosophila melanogaster acetylcholinesterase (R-DmAChE) as enzyme and indoxyl acetate as substrate. The visible chromogenic strip had the advantages identical to those of commonly used lateral flow assays (LFAs) with utmost simplicity in sample loading and result observation. After optimization, depending on the color intensity (CI) values, the well-established assay has the capabilities of both qualitative measurement via naked eyes and quantitative analysis by colorimetric reader with the desirable IC(50) values against the tested six insecticides (0.06μgmL(-1) of carbofuran, 0.28μgmL(-1) of methomyl, 0.03μgmL(-1) of dichlorvos, 31.6μgmL(-1) of methamidophos, 2.0μgmL(-1) of monocrotophos, 6.3μgmL(-1) of omethoate). Acceptable matrix effects and satisfactory detection performance were confirmed by in-parallel LC-MS/MS analysis in different vegetable varieties at various spiked levels of 10(-3) to 10(1)μgg(-1). Overall, the testified suitability and applicability of this novel platform meet the requirements for practical use in food safety management and environmental monitoring, especially in the developing world.

Dosimetric Impact of Breathing Motion in Lung Stereotactic Body Radiotherapy Treatment Using Image-Modulated Radiotherapy and Volumetric Modulated Arc Therapy

International Journal of Radiation Oncology, Biology, Physics. Feb, 2012  |  Pubmed ID: 22365622

PURPOSE: The objective of this study was to investigate the influence of tumor motion on dose delivery in stereotactic body radiotherapy (SBRT) for lung cancer, using fixed field intensity- modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). METHODS AND MATERIALS: For each of 10 patients with stage I/II non-small-cell pulmonary tumors, a respiration-correlated four-dimensional computed tomography (4DCT) study was carried out. The internal target volume was delineated on the maximum intensity projection CT, which was reconstructed from the 4DCT dataset. A 5-mm margin was used for generation of the planning target volume. VMAT and five-field IMRT plans were generated using Pinnacle(3) SmartArc and direct machine parameter optimization, respectively. All plans were generated for an Elekta Synergy linear accelerator using 6-MV photons. Simulation was performed to study the interplay between multileaf collimator (MLC) sequences and target movement during the delivery of VMAT and IMRT. For each plan, 4D dose was calculated using deformable image registration of the 4DCT images. Target volume coverage and doses to critical structures calculated using 4D methodology were compared with those calculated using 3D methodology. RESULTS: For all patients included in this study, the interplay effect was found to present limited impact (less than 1% of prescription) on the target dose distribution, especially for SBRT, in which fewer fractions (three fractions) are delivered. Dose to the gross tumor volume (GTV) was, on average, slightly decreased (1% of prescription) in the 4D calculation compared with the 3D calculation. The motion impact on target dose homogeneity was patient-dependent and relatively small. CONCLUSIONS: Both VMAT and IMRT plans experienced negligible interplay effects between MLC sequence and tumor motion. For the most part, the 3D doses to the GTV and critical structures provided good approximations of the 4D dose calculations.

Sleep Disturbances in Juvenile Myoclonic Epilepsy: A Sleep Questionnaire-based Study

Epilepsy & Behavior : E&B. Feb, 2012  |  Pubmed ID: 22366052

Sleep and epilepsy share a complex pathophysiological association. Juvenile myoclonic epilepsy (JME) is a common sleep-sensitive epilepsy in which the effect of seizures could have therapeutic implications in terms of sleep disturbances and seizure control. This study aimed to analyze the effect of epilepsy on sleep in patients with JME. Fifty patients on valproic acid (VPA) monotherapy, and age- and gender-matched controls were recruited into this prospective, hospital-based, case-control study after informed consent and screening for inclusion criteria. They underwent a detailed clinical assessment, electroencephalogram (EEG) and neuroimaging, and were administered validated sleep questionnaires, which included the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI) and NIMHANS Sleep Disorders Questionnaire. The patient and control groups had identical numbers of males and females (M: F=22: 28), without any significant difference in the age and body mass index (BMI). The clinical profile of JME was similar to published literature while the prevalence of EEG abnormalities was less compared to similar studies. The mean ESS and PSQI scores and the number of subjects with abnormal scores on one or both questionnaires were significantly more in patients. Patients had a higher prevalence of sleep disturbances, insomnia and excessive daytime somnolence. No significant seizure- or treatment-related factors influencing sleep could be identified. This study, the first of its kind, revealed that patients with JME have significant sleep disturbances characterized by excessive daytime sleepiness and disturbed night sleep, despite adequate medications and good seizure control. The role of VPA in the genesis of these symptoms needs clarification.

Oncomir MiR-125b Regulates Hematopoiesis by Targeting the Gene Lin28A

Proceedings of the National Academy of Sciences of the United States of America. Feb, 2012  |  Pubmed ID: 22366319

MicroRNA-125b (miR-125b) is up-regulated in patients with leukemia. Overexpression of miR-125b alone in mice causes a very aggressive, transplantable myeloid leukemia. Before leukemia, these mice do not display elevation of white blood cells in the spleen or bone marrow; rather, the hematopoietic compartment shows lineage-skewing, with myeloid cell numbers dramatically increased and B-cell numbers severely diminished. miR-125b exerts this effect by up-regulating the number of common myeloid progenitors while inhibiting development of pre-B cells. We applied a miR-125b sponge loss of function system in vivo to show that miR-125b physiologically regulates hematopoietic development. Investigating the mechanism by which miR-125b regulates hematopoiesis, we found that, among a panel of candidate targets, the mRNA for Lin28A, an induced pluripotent stem cell gene, was most repressed by miR-125b in mouse hematopoietic stem and progenitor cells. Overexpressing Lin28A in the mouse hematopoietic system mimicked the phenotype observed on inhibiting miR-125b function, leading to a decrease in hematopoietic output. Relevant to the miR-125b overexpression phenotype, we also found that knockdown of Lin28A led to hematopoietic lineage-skewing, with increased myeloid and decreased B-cell numbers. Thus, the miR-125b target Lin28A is an important regulator of hematopoiesis and a primary target of miR-125b in the hematopoietic system.

Cataract Surgery in Primary Angle Closure: Can It Replace Iridectomy?

Journal of Glaucoma. Feb, 2012  |  Pubmed ID: 22366698

Plateau Iris in Open-angle Glaucoma?

Journal of Glaucoma. Feb, 2012  |  Pubmed ID: 22366699

Combination of Pan-histone Deacetylase Inhibitor and Autophagy Inhibitor Exerts Superior Efficacy Against Triple-negative Human Breast Cancer Cells

Molecular Cancer Therapeutics. Feb, 2012  |  Pubmed ID: 22367781

Histone deacetylase (HDAC) inhibitors (HDIs) induce endoplasmic reticulum (ER) stress and apoptosis, while promoting autophagy, which promotes cancer cell survival when apoptosis is compromised. Here, we determined the in vitro and in vivo activity of the combination of the pan-HDI panobinostat (PS) and the autophagy inhibitor chloroquine (CL) against human estrogen/progesterone receptor and HER2 (triple)-negative breast cancer (TNBC) cells. Treatment of MB-231 and SUM159PT cells with PS disrupted the hsp90/histone deacetylase 6/HSF1/p97 complex, resulting in the upregulation of heat shock proteins. This was accompanied by the induction of enhanced autophagic flux as evidence by increased expression of LC3B-II and the degradation of the autophagic substrate p62. Treatment with PS also induced the accumulation and co-localization of p62 with LC3B-II in cytosolic foci as evidenced by immunofluorescent confocal microscopy. Inhibition of PS-induced autophagic flux by CL markedly induced the accumulation of polyubiquitylated proteins and p62, caused synergistic cell death of MB-231 and SUM159PT cells and inhibited mammosphere formation in MB-231 cells, compared to treatment with each agent alone. Finally, in mouse mammary fat pad xenografts of MB-231 cells, a tumor size-dependent induction of heat shock response, ER stress and autophagy was observed. Co-treatment with PS and CL resulted in the reduced tumor burden and increased the survival of MB-231 breast cancer xenografts. Collectively, our findings demonstrate that co-treatment with an autophagy inhibitor and pan-HDI e.g., CL and PS results in accumulation of toxic polyubiquitylated proteins, exerts superior inhibitory effects on TNBC cell growth and increases the survival of TNBC xenografts.

Pharm D: A New Concept in India

Journal of Pharmacy & Bioallied Sciences. Jan, 2012  |  Pubmed ID: 22368406

Acute Pancreatitis

Disease-a-month : DM. Mar, 2012  |  Pubmed ID: 22370054

Gastroprotective Effect of Byrsonima Sericea DC Leaf Extract Against Ethanol-induced Gastric Injury and Its Possible Mechanisms of Action

Anais Da Academia Brasileira De Ciencias. Feb, 2012  |  Pubmed ID: 22370554

Byrsonima sericea leaves are extensively used in folk medicine in Brazil against gastric disorders. This study investigated the chemical constituents of B. sericea leaf ethanolic extract (BSLE) and its potential gastroprotective activity, with its possible mechanism of the action using ethanol to induce gastric mucosal damage in mice. The phytochemical analysis was carried out to identify the active constituents present in the extract, and the HPLC analysis was performed for the identification of flavonoids. BSLE at oral doses of 125, 250 and 500 mg/kg markedly attenuated the ethanol-evoked gastric lesions by 53.2, 84.9 and 87.6 %, respectively. The BSLE (250 mg/kg) prevented the depletion of gastric mucus and gastric mucosal nonproteic-sulfhydryl groups, SOD and CAT, as well as the increase in the MDA content promoted by absolute ethanol. Moreover, the effect of BSLE against ethanol damage was found to be significantly reduced in mice pretreated with Capsazepine (i.p.), L-NAME (i.p.) or glibenclamide (i.p.), the respective blockers/inhibitors of TRPV1, NO synthase and K+ATP channel. The phytochemical investigation on BSLE revealed the presence of flavonoids rutin, isoquercitrin, kaempferol 3-O-rutinoside and quercetin, which are compounds well known for their antioxidant and gastroprotective properties. These results suggest that BSLE affords gastroprotection through multiple mechanisms, which may be helpful in the treatment of pathologies associated with gastric dysfunctions.

Factor VIIa Binding to Endothelial Cell Protein C Receptor: Differences Between Mouse and Human Systems

Thrombosis and Haemostasis. Feb, 2012  |  Pubmed ID: 22370814

Recent in vitro studies have shown that the zymogen and activated form of factor (F)VII bind to endothelial cell protein C receptor (EPCR). At present, there is no evidence that FVIIa binds to EPCR on vascular endothelium in vivo in the presence of circulating protein C, a primary ligand for EPCR. The present study was carried out to investigate the interaction of murine and human ligands with murine EPCR both in vivo and in vitro . Measurement of endogenous plasma levels of FVII in wild-type, EPCR-deficient and EPCR-over expressing mice showed slightly lower levels of FVII in EPCR-over expressing mice. However, infusion of high concentrations of competing ligands, either human APCi or FVIIai, to EPCR-over expressing mice failed to increase plasma levels of mouse FVII whereas they increased the plasma levels of protein C by two- to three-fold. Examining the association of exogenously administered mouse FVIIa or human FVIIa by immunohistochemistry revealed that human, but not murine FVIIa, binds to the murine endothelium in an EPCR-dependent manner. In vitro binding studies performed using surface plasmon resonance and endothelial cells revealed that murine FVIIa binds murine EPCR negligibly. Human FVIIa binding to EPCR, particularly to mouse EPCR, is markedly enhanced by availability of Mg2+ ions. In summary, our data show that murine FVIIa binds poorly to murine EPCR, whereas human FVIIa binds efficiently to both murine and human EPCR. Our data suggest that one should consider the use of human FVIIa in mouse models to investigate the significance of FVIIa and EPCR interaction.

Physiological and Molecular Analysis of the Interaction Between Aluminium Toxicity and Drought Stress in Common Bean (Phaseolus Vulgaris)

Journal of Experimental Botany. Feb, 2012  |  Pubmed ID: 22371077

Aluminium (Al) toxicity and drought are two major factors limiting common bean (Phaseolus vulgaris) production in the tropics. Short-term effects of Al toxicity and drought stress on root growth in acid, Al-toxic soil were studied, with special emphasis on Al-drought interaction in the root apex. Root elongation was inhibited by both Al and drought. Combined stresses resulted in a more severe inhibition of root elongation than either stress alone. This result was different from the alleviation of Al toxicity by osmotic stress (-0.60 MPa polyethylene glycol) in hydroponics. However, drought reduced the impact of Al on the root tip, as indicated by the reduction of Al-induced callose formation and MATE expression. Combined Al and drought stress enhanced up-regulation of ACCO expression and synthesis of zeatin riboside, reduced drought-enhanced abscisic acid (ABA) concentration, and expression of NCED involved in ABA biosynthesis and the transcription factors bZIP and MYB, thus affecting the regulation of ABA-dependent genes (SUS, PvLEA18, KS-DHN, and LTP) in root tips. The results provide circumstantial evidence that in soil, drought alleviates Al injury, but Al renders the root apex more drought-sensitive, particularly by impacting the gene regulatory network involved in ABA signal transduction and cross-talk with other phytohormones necessary for maintaining root growth under drought.

Excellent Outcome of Matched Unrelated Donor Transplantation in Paediatric Aplastic Anaemia Following Failure with Immunosuppressive Therapy: a United Kingdom Multicentre Retrospective Experience

British Journal of Haematology. Feb, 2012  |  Pubmed ID: 22372373

We retrospectively analysed the outcome of consecutive children with idiopathic severe aplastic anaemia in the United Kingdom who received immunosuppressive therapy (IST) or matched unrelated donor (MUD) haematopoietic stem cell transplantation (HSCT). The 6-month cumulative response rate following rabbit antithymocyte globulin (ATG)/ciclosporin (IST) was 32·5% (95% CI 19·3-46·6) (n = 43). The 5-year estimated failure-free survival (FFS) following IST was 13·3% (95% confidence interval [CI] 4·0-27·8). In contrast, in 44 successive children who received a 10-antigen (HLA-A, -B, -C, -DRB1, -DQB1) MUD HSCT there was an excellent estimated 5-year FFS of 95·01% (95% CI 81·38-98·74). Forty of these children had failed IST previously. HSCT conditioning was a fludarabine, cyclophosphamide and alemtuzumab (FCC) regimen and did not include radiotherapy. There were no cases of graft failure. Median donor chimerism was 100% (range 88-100%). A conditioning regimen, such as FCC that avoids total body irradiation is ideally suited in children. Our data suggest that MUD HSCT following IST failure offers an excellent outcome and furthermore, if a suitable MUD can be found quickly, MUD HSCT may be a reasonable alternative to IST.

Cytokine Gene Polymorphisms in the Susceptibility to Acute Coronary Syndrome

Genetic Testing and Molecular Biomarkers. Feb, 2012  |  Pubmed ID: 22372709

Aim: Acute coronary syndrome (ACS) is an inflammatory disease. Cytokines are the central regulators of inflammation and may be a cause or marker of atherosclerosis. Accumulating evidence suggests that polymorphisms at promoter regions of various cytokine genes are known to be associated with their expression levels. In the present study we investigated whether variants at -1082G→A (rs1800896) and -592C→A (rs1800872) of interleukin-10 (IL-10), -1188A→C (rs3212227) of IL-12 p40, -308G→A of tumor necrosis factor-α (TNF-α) (rs1800629), -174G→C of IL-6 (rs1800795) and +874A→T of interferon-γ (IFN-γ) genes (rs2430561) are associated with ACS. Materials and Methods: DNA samples were collected from 1083 subjects and IL-10-1082G→A, -592A→C, TNF-α-308G→A, IL-12 p40-1188 A→C, and IFN-γ+874A→T polymorphisms were identified by amplified refractory mutation system polymerase chain reaction and IL-6-174 G/C, restriction fragment length polymorphism based on standard methods. Results: Six hundred and fifty one ACS patients along with 432 age and sex matched controls were analyzed for various gene polymorphisms. The "low-producer" IL-10-1082 AA (χ(2)=9.45; p=0.0021; odds ratio [OR]=1.472; 95% confidence interval [CI]=1.15-1.884), "high producer" IL-10-592 CC (χ(2)=39.42; p=0.001, OR=2.26; 95% CI=1.748-2.292), "low producer"IFN-γ+874AA (χ(2)=28; p<0.00154; OR=2.36 & 95% CI=1.713-3.251), and "high producer" TNF-α -308AA (χ(2)=3.213, p=0.073; OR=1.515) genotypes may be responsible for the regulation of immune response leading to inflammation in ACS patients. However, -1188 of the IL-12 gene was not associated with the disease. Conclusion: The polymorphisms at -308G→A of TNF-α, -174G→C of IL-6, +874A→T of IFN-γ and -1082G→A, and -592C→A of IL-10 genes evaluated in the present study are important risk factors for the development of ACS in the South Indian population from Andhra Pradesh. The better understanding of these variants conferring susceptibility to ACS may aid in early diagnosis and development of new methods to create personalized medicine.

Influence of Endothelial Cell Protein C Receptor on Plasma Clearance of Factor VIIa

Journal of Thrombosis and Haemostasis : JTH. Feb, 2012  |  Pubmed ID: 22372829

Author Reply

Ophthalmology. Feb, 2012  |  Pubmed ID: 22305318

Percutaneous Needle Vs Surgical Breast Biopsy: Previous Allegations of Overuse of Surgery Are in Error

Journal of the American College of Radiology : JACR. Feb, 2012  |  Pubmed ID: 22305700

A recent paper in the American Journal of Surgery reported that surgery is used for 30% of breast biopsies, an excessive number. The investigators' stated biopsy volume included Current Procedural Terminology(®) code 19125 ("excision of breast lesion identified by preoperative placement of radiological marker, open"). However, this code may often be used when a surgeon's primary intention is not biopsy but rather excision of a lesion. Therefore, the reported results may overstate the percentage of biopsies performed as surgical procedures. The aim of this study was to more accurately assess the use of percutaneous core needle biopsy (PNB) compared with surgical biopsy.

Dramatically Increased Musculoskeletal Ultrasound Utilization from 2000 to 2009, Especially by Podiatrists in Private Offices

Journal of the American College of Radiology : JACR. Feb, 2012  |  Pubmed ID: 22305701

Over the past two decades, musculoskeletal (MSK) ultrasound has emerged as an effective means of diagnosing MSK pathologies. However, some insurance providers have expressed concern about increased MSK ultrasound utilization, possibly facilitated by the low cost and ready availability of ultrasound technology. The purpose of this study was to document trends in MSK ultrasound utilization from 2000 to 2009 within the Medicare population.

Elevated Vitamin B(12) Levels in Autoimmune Lymphoproliferative Syndrome Attributable to Elevated Haptocorrin in Lymphocytes

Clinical Biochemistry. Jan, 2012  |  Pubmed ID: 22306884

OBJECTIVE: Identify the etiology of elevated B(12) in autoimmune lymphoproliferative syndrome (ALPS). DESIGN: Peripheral blood of ALPS patients with elevated B(12) and controls were evaluated. RESULTS: Total and holo-haptocorrin (HC) levels were 26- and 23-fold higher in ALPS patients, respectively. No abnormal B(12)-binding proteins were found. Western blot revealed HC in lymphocyte lysates only from ALPS patients. CONCLUSION: Elevated concentrations of B(12) found in ALPS patients were due to increased lymphocyte expression of HC.

Particle Size Distribution of Ambient Aerosols in an Industrial Area

Bulletin of Environmental Contamination and Toxicology. Feb, 2012  |  Pubmed ID: 22307732

Aerosol samples of PM(10) and PM(2.5) were collected from 38 sampling locations in and around the industrial area. The 24 h average mass concentration of PM(10) and PM(2.5) was 137.5 and 61.5 μg/m(3) respectively during summer, 122 and 97.5 μg/m(3) respectively in winter and 70 and 54 μg/m(3) respectively during post monsoon season. The relative contribution of coarse, fine and ultrafine particle to ambient air was analyzed for its temporal and seasonal variability in an industrialized area. This paper aims to establish baseline between PM(10) and PM(2.5) mass concentration levels.

The Effect of Different Dialysate Magnesium Concentrations on QTc Dispersion in Hemodialysis Patients

Renal Failure. Feb, 2012  |  Pubmed ID: 22299661

Background: Electrolyte changes during dialysis affect corrected QT (QTc) and QTc dispersion (QTcd), a surrogate marker of arrhythmogenicity. The impact of magnesium on QTcd is not clear. Methods: Twenty-two stable patients on maintenance hemodialysis were enrolled in this study. Each underwent two consecutive hemodialysis sessions at least 2 days apart, the first against normal magnesium dialysate (with magnesium at 1.8 mg/dL) followed by a low magnesium dialysate (with magnesium at 0.6 mg/dL). Pre- and post-dialysis weights, blood pressure, electrolytes, and 12-lead surface EKG were recorded. The QT interval and the QTcd were calculated before and after dialysis in both sessions. Results: Of 22 patients, 16 were female. The mean age ± SD was 53.7 ± 18.0 years. The mean change of QTcd (pre- vs. post-dialysis) was 9.5 ms (p = 0.120) and 9.3 ms (p = 0.145) in low and normal magnesium groups, respectively. Using univariate analysis, there was a statistically significant decrease in the mean blood pressure, weight, potassium, magnesium, and QTc interval post-dialysis (compared to pre-dialysis) in both groups (p ≤ 0.049). Post-dialysis concentrations of sodium and calcium were unchanged (compared to pre-dialysis) but bicarbonate increased with both dialysate groups (p < 0.001). The mean change of QTcd was not significant pre- versus post-dialysis by univariate analysis in either group. Multiple linear regression analysis adjusting for pertinent factors did not change the results in either of the two groups. Conclusion: Using a low magnesium dialysate bath in hemodynamically stable hemodialysis patients without preexisting advanced cardiac disease does not significantly impact QTcd.

Chemical Composition of Five Wild Edible Mushrooms Collected from Southwest China and Their Antihyperglycemic and Antioxidant Activity

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. Jan, 2012  |  Pubmed ID: 22300772

Evaluation of the chemical composition and antihyperglycemic and antioxidant activity of five wild edible mushrooms (Clitocybe maxima, Catathelasma ventricosum, Stropharia rugoso-annulata, Craterellus cornucopioides and Laccaria amethystea) from Southwest China. The chemical composition assay includes proximate analysis (moisture, ash, crude protein, crude fat, total carbohydrates and total energy), bioactive compounds analysis (total phenolic, flavonoid, ascorbic acid, ergosterol, tocopherol), fatty acid analysis, amino acid analysis, phenolic compounds analysis and mineral analysis of these mushrooms. Furthermore, assays of α-glucosidase inhibitory and α-amylase inhibitory activity were used for evaluating antihyperglycemic activity of the mushrooms, and assays of reducing power, chelating effect on ferrous ions, scavenging effect on hydroxyl free radicals and 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity were used for evaluating antioxidant activity of the mushrooms. Based on the results, ethanolic and aqueous extract of these mushroom all showed antihyperglycemic and antioxidant potential. In particular, the aqueous extract of C. ventricosum revealed the highest α-glucosidase inhibitory activity (EC50 value 2.74μg/mL), DPPH radical scavenging activity (EC50 value 2.86mg/mL) and reducing power (EC50 value 0.96mg/mL), while the aqueous extract of L. amethystea showed the highest α-amylase inhibitory activity (EC50 value 4.37μg/mL) and metal chelating activity (EC50 value 2.13mg/mL).

Nanoporous Multilayer Poly(l-glutamic Acid)/chitosan Microcapsules for Drug Delivery

International Journal of Pharmaceutics. Jan, 2012  |  Pubmed ID: 22301425

Nanoporous poly(l-glutamic acid)/chitosan (PLGA/CS) multilayer microcapsules were fabricated by layer-by-layer (LbL) assembly using the porous silica particles as sacrificial templates. The LbL assembled nanoporous PLGA/CS microcapsules were characterized by Zeta-potential analyzer, FTIR, TGA, SEM, TEM and CLSM. 5-Fluorouracil (5-FU) was chosen as model drug. The drug loading content of PLGA/CS microcapsules depends on loading time, loading temperature, pH value and NaCl concentration. High loading capacity of microcapsules can be achieved by simply adjusting pH value and salt concentration. Moreover, 5-Fu loaded microcapsules take on a sustained release behavior, especially in an acid solution, in contrast to burst release of bare 5-Fu. The kinetics of 5-Fu release from PLGA/CS microcapsules conforms to Korsmeyer-Peppas and Baker-Lonsdale models, the mechanism of which can be ascribed to priority of drug diffusion and subordination of polymer degradation. The MTT cytotoxicity assay in vitro reveals the satisfactory anticancer activity of the drug-loaded PLGA/CS microcapsules. Therefore, the novel nanoporous PLGA/CS microcapsules is expected to find application in drug delivery systems.

Photoinduced Electron Transfer Between a Donor and an Acceptor Separated by a Capsular Wall

Chemical Communications (Cambridge, England). Feb, 2012  |  Pubmed ID: 22301470

The efficient photoinduced electron transfer from a stilbene derivative incarcerated within a negatively charged organic nanocapsule to positively charged acceptors (methyl viologen and a pyridinium salt) adsorbed outside and the back electron transfer were controlled by supramolecular effects.

Expression of OCT3/4 in Renal Medullary Carcinoma Represents a Potential Diagnostic Pitfall

The American Journal of Surgical Pathology. Jan, 2012  |  Pubmed ID: 22301499

Renal medullary carcinoma (RMC) is a rare aggressive renal tumor that classically afflicts young black patients with sickle cell trait. The tumor shows overlapping pathologic and clinical characteristics with collecting duct carcinoma and urothelial carcinoma, which often results in a diagnostic conundrum. When the tumor presents in a metastatic site in the absence of a history of renal tumor, germ-cell tumor is often a primary diagnostic consideration, given the young age of most patients. OCT3/4 is an immunohistochemical marker that is routinely used in clinical practice and is widely considered to be a specific marker for germ-cell tumor. We studied the pathologic and immunohistochemical characteristics of 14 cases of RMC. Immunohistochemical staining for OCT3/4 staining was noted in 10/14 RMCs with strong nuclear staining in 8 cases and was absent in all cases of collecting duct carcinoma and urothelial carcinoma. OCT3/4 expression is not specific to germ-cell tumor and is seen in the majority of RMC cases. Caution must be exercised in interpreting the presence of OCT3/4 staining in a poorly differentiated neoplasm, especially at a metastatic site as a germ-cell tumor, as this may represent a potential diagnostic pitfall.

Equol Status and Blood Lipid Profile in Hyperlipidemia After Consumption of Diets Containing Soy Foods

The American Journal of Clinical Nutrition. Mar, 2012  |  Pubmed ID: 22301925

Recent analyses have challenged the effectiveness of soy foods as part of a cardiovascular risk reduction diet.

Pharmacokinetics and Tissue and Tumor Exposure of CP-31398, a P53-stabilizing Agent, in Rats

Cancer Chemotherapy and Pharmacology. Feb, 2012  |  Pubmed ID: 22302406

PURPOSE: CP-31398 (N'-[2-[(E)-2-(4-methoxyphenyl)ethenyl]quinazolin-4-yl]-N,N-dimethylpropane-1,3-diamine hydrochloride) is one of the new class of agents that can stabilize the DNA-binding domain of p53 and thereby maintain the activity of p53 as a tumor suppressor and transcription factor. Through its activity as a p53 stabilizer, CP-31398 demonstrates significant cancer preventive and therapeutic activity in several in vivo animal models. The objective of the current study was to describe the pharmacokinetic profile and tissue distribution of this novel agent following intravenous or oral (gavage and dietary) administration. METHODS: CP-31398 was administered to male CD and F344 rats as a single intravenous bolus dose or by daily oral gavage dosing. Male F344 rats also received drug as an ad libitum dietary supplement. Plasma, liver, skin, colon, and colon tumor samples were collected after oral dosing. Concentrations of CP-31398 in plasma and tissue samples were analyzed using LC-MS/MS, and the resultant data were subjected to a non-compartmental pharmacokinetic analysis. RESULTS: Bioavailability (12-32%), elimination half-life (14-20 h), clearance (4.2-4.8 l/h/kg), and volume of distribution (70-82 l/kg) were determined. Tissue levels of CP-31398 after oral (gavage or diet) administration were several orders of magnitude higher than were corresponding plasma concentrations; CP-31398 levels were especially high in colon and liver. Levels of CP-31398 in tissues were higher after gavage dosing than after dietary administration. CONCLUSIONS: CP-31398 is bioavailable and has a relatively long elimination half-life, which supports the achievement of plasma steady-state levels with a once daily dosing regimen. CP-31398 exhibits a dramatically high volume of distribution, which is consistent with its tissue concentrations being much higher than corresponding plasma levels. It is accumulated in colon tumor tissues, albeit at lower concentrations than found in liver, skin, and colon.

Cloudy Peritoneal Fluid Attributable to Non-dihydropyridine Calcium Channel Blocker

Peritoneal Dialysis International : Journal of the International Society for Peritoneal Dialysis. Jan, 2012  |  Pubmed ID: 22302929

Development and Calibration of a Standard for the Protein Content of Granulocyte Colony-stimulating Factor Products

Biologicals : Journal of the International Association of Biological Standardization. Jan, 2012  |  Pubmed ID: 22296785

This collaborative study characterizes a homogeneous standard for the protein content determination of granulocyte colony-stimulating factor (G-CSF) products with traceability of the measurement. The Kjeldahl method was used to determine the average protein content of G-CSF bulk as 2.505 mg/ml (95% C.I: 2.467-2.543 mg/ml, GCV 4.0%). Using G-CSF bulk as a traceability benchmark, the protein content of the final freeze-dried standard using reverse phase HPLC (RP-HPLC) was 215.4 μg protein per ampoule (95% C.I: 212.407-218.486 μg/ampoule, GCV 3.4%). A comparative study showed that there was no difference between using Filgrastim CRS (European Pharmacopeia G-CSF reference standard) and freeze-dried homogeneous standard when quantifying G-CSF protein content by RP-HPLC (P > 0.05). However, there were significant differences in the G-CSF protein content obtained using a serum albumin standard by Lowry assay and a G-CSF standard with RP-HPLC. Therefore, use of RP-HPLC with a freeze-dried homogeneous standard would eliminate the systematic errors introduced when using a serum albumin standard because of the differences in protein composition between the standard and the sample. It would also be helpful to use this method to compare the quality of G-CSF biosimilar products in situations where the protein content has been calibrated using various standards.

Viruses: Sophisticated Biological Machines

Advances in Experimental Medicine and Biology. 2012  |  Pubmed ID: 22297507

Virus infection involves coordination of a series of molecular machines, including entry machines, replication machines, assembly machines, and genome packaging machines, leading to the production of infectious virions. This chapter provides an introduction to various viral molecular machines described in this book.

The Bacteriophage DNA Packaging Machine

Advances in Experimental Medicine and Biology. 2012  |  Pubmed ID: 22297528

Large dsDNA bacteriophages and herpesviruses encode a powerful ATP-driven DNA-translocating machine that encapsidates a viral genome into a preformed capsid shell or prohead. The key components of the packaging machine are the packaging enzyme (terminase, motor) and the portal protein that forms the unique DNA entrance vertex of prohead. The terminase complex, comprised of a recognition subunit (small terminase) and an endonuclease/translocase subunit (large terminase), cuts viral genome concatemers. The terminase-viral DNA complex docks on the portal vertex, assembling a motor complex containing five large terminase subunits. The pentameric motor processively translocates DNA until the head shell is full with one viral genome. The motor cuts the DNA again and dissociates from the full head, allowing head-finishing proteins to assemble on the portal, sealing the portal, and constructing a platform for tail attachment. A body of evidence from molecular genetics and biochemical, structural, and biophysical approaches suggests that ATP hydrolysis-driven conformational changes in the packaging motor (large terminase) power DNA motion. Various parts of the motor subunit, such as the ATPase, arginine finger, transmission domain, hinge, and DNA groove, work in concert to translocate about 2 bp of DNA per ATP hydrolyzed. Powerful single-molecule approaches are providing precise delineation of steps during each translocation event in a motor that has a speed as high as a millisecond/step. The phage packaging machine has emerged as an excellent model for understanding the molecular machines, given the mechanistic parallels between terminases, helicases, and numerous motor proteins.

Effect of Nonsurgical Periodontal Therapy on Crevicular Fluid and Serum Glutathione Peroxidase Levels

Disease Markers. Jan, 2012  |  Pubmed ID: 22297597

Background: Plasma glutathione peroxidase (eGPx) is an important selenium containing antioxidant in human defense against oxidative stress. While crevicular fluid (GCF) eGPx levels and its association with periodontal disease is well documented, there is no data on correlation of GCF and serum eGPx levels in chronic periodontitis. Hence this study was undertaken to further probe into the role of oxidative stress in periodontal diseases and effect of nonsurgical periodontal therapy (NSPT) by correlating GCF and serum levels of eGPx. Materials and methods: Thirty subjects (16-Males and 14-Females; age: 30-38 years) participated in the study. The subjects were divided, based on gingival index, probing pocket depth and clinical attachment level into: Healthy (group-1, n=10), Gingivitis (group-2, n=10) and Periodontitis (group-3, n=10). Chronic periodontitis patients after NSPT constituted group 4. GCF and serum samples collected from each subject were quantified for eGPx levels using Enzyme linked Immunosorbent Assay. Results: The mean eGPx concentrations increased from health (14.01 ng/μl and 78.26 ng/ml) to gingivitis (22.86 ng/μl and 90.44 ng/ml) and then to periodontitis (29.89 ng/μl and 103.43 ng/ml), in GCF and serum respectively. After NSPT, there was statistically significant reduction in eGPx concentration in GCF and serum (19.41 ng/μl and 85.21 ng/ml). Further, all the GCF eGPx values showed a positive correlation to that of serum eGPx level.Conclusion: Thus, increased eGPx concentration in GCF can be considered as an indicator of local increase in oxidative stress. While, increase in serum eGPx levels indicates that periodontal disease can also lead to increased oxidative stress at the systemic level.

Differences of Z Chromosome and Genomic Expression Between Early- and Late-feathering Chickens

Molecular Biology Reports. Feb, 2012  |  Pubmed ID: 22297689

One duplicated segment on chicken Z chromosome is a causal mutation to the late-feathering phenotype. However, understanding biological process of the late-feathering formation is also of interest to chicken breeding and feather development theory. One hundred and thirty-seven valid single nucleotide polymorphisms (SNPs) from an SNP database were used to perform an association study of the Z chromosome in Xinghua chickens. Two SNPs, which were respectively on 9607480 bp and 10607757 bp, were significantly associated with feathering phenotypes. This result indicated the causal mutation of the late-feathering formation in Xinghua chickens was consistent with the previous report which showed the late-feathering locus ranged 9966364-10142688 bp on Z chromosome. Microarray expressions were implemented for six 1-day-old female Xinghua chicks. Compared to the early-feathering chicks, there were 249 and 83 upregulated and downregulated known genes in the late-feathering chicks. Forty-one genes were expressed in late-feathering chicks, but not in early-feathering ones. At least 14 significantly differentially expressed genes were directly related to keratin. In the region of the sex-linked feathering gene, only prolactin receptor (PRLR) gene was a significantly differentially expressed gene. Expression of PRLR in late-feathering chicks was 1.78-fold as that in early-feathering chicks. Late-feathering Wenchang chicks also had higher expression level of PRLR than early-feathering ones. This study suggested that increasing PRLR expression that resulted from the special variant on chicken Z chromosome caused the late-feathering phenotype.

A Hoxb13-driven Reverse Tetracycline Transactivator System for Conditional Gene Expression in the Prostate

The Prostate. Feb, 2012  |  Pubmed ID: 22297979

BACKGROUND: Genetically engineered mouse models play important roles in analyses of prostate development and pathobiology. While constitutive genetic gain- and loss-of-function models have contributed significantly to our understanding of molecular events driving these processes, the availability of a tightly regulated inducible expression system could extend the utility of transgenic approaches. Here, we describe the development of a Tet-regulatory system that employs Hoxb13 transcriptional control elements to direct reverse tetracycline transactivator (rtTA) expression in the prostate. METHODS: Using recombineering technology, the rtTA gene was placed under Hoxb13 cis-regulatory transcriptional control in the context of a 218-kb bacterial artificial chromosome. F(1) offspring carrying the Hoxb13-rtTA transgene were bred to a Tetracycline operator-Histone 2B-Green Fluorescent Protein (TetO-H2BGFP) responder line. Detailed reporter gene expression analyses, including doxycycline (Dox) induction and withdrawal kinetics, were performed in Hoxb13-rtTA|TetO-H2BGFP double transgenic adult mice and embryos. RESULTS: Dox-dependent GFP expression was observed exclusively in the prostate and distal colon epithelia of double transgenic mice. Reporter gene mRNA was detected in the prostate within 6 hr of Dox exposure, and was extinguished within 24 hr after Dox withdrawal. Furthermore, Dox-induced reporter gene expression persisted after castration. CONCLUSIONS: The Hoxb13-rtTA transgenic system provides a powerful tool for conditional Tet operator-driven transgene expression in the normal prostate and during disease progression. Used in conjunction with other prostate pathology models, these mice will enable precise, temporally controlled analyses of gene function and can provide opportunities for detailed analyses of molecular events underlying prostate diseases. Prostate © 2012 Wiley Periodicals, Inc.

Composites of Graphene and Other Nanocarbons with Organogelators Assembled Through Supramolecular Interactions

Chemistry (Weinheim an Der Bergstrasse, Germany). Mar, 2012  |  Pubmed ID: 22298373

Carbon nanomaterials (CNMs), such as exfoliated graphene (EG), long-chain functionalized EG, single-walled carbon nanotubes (SWNTs), and fullerene (C(60) ), have been investigated for their interaction with two structurally different gelators based on all-trans tri-p-phenylenevinylene bis-aldoxime (1) and n-lauroyl-L-alanine (2) both in solution and in supramolecular organogels. Gelation occurs in toluene through hydrogen bonding and van der Waals interactions for 1 and 2 in addition to π-π stacking specifically in the case of 1. These nanocomposites provide a thorough understanding in terms of molecular-level interactions of dimensionally different CNMs with structurally different gelators. The presence of densely wrapped CNMs encapsulated fibrous network in the resulting composites is evident from various spectroscopic and microscopic studies, indicating the presence of supramolecular interactions. Concentration- and temperature-dependent UV/Vis and fluorescence spectra show that CNMs promote aggregation of the gelator molecules, leading to hypochromism and quenching of the fluorescence intensity. Thermotropic mesophases of 1 are altered by the inclusion of a small amount of CNMs. The gel-CNM composites show increased electrical conductivity compared with that of the native organogel. Rheological studies of the composites demonstrate the formation of rigid and viscoelastic solidlike assembly due to reinforced aggregation of the gelators on CNMs. Synergistic behavior is observed in case of the composite gel of 1, containing a mixture of EG and SWNT, when compared with other mixtures of CNMs in all combinations with EG. This affords new nanocomposites with interesting optical, thermal, electrical, and mechanical properties.

Are Endothelial Progenitor Cells a Prognostic Factor in Patients with Heart Failure?

Expert Review of Cardiovascular Therapy. Feb, 2012  |  Pubmed ID: 22292873

For the last two decades, endothelial progenitor cells (EPCs) have been proposed as a novel prognostic marker and potential therapeutic target in patients with cardiovascular diseases. EPCs are involved in the process of adult vasculogenesis and repair of dysfunctional endothelium. Endothelial dysfunction has been documented in the peripheral and coronary arteries of chronic heart failure (HF) patients, and has proved to be an independent predictor of morbidity and mortality in HF patients. This has led researchers to analyze the association of EPCs and disease severity in HF patients. In this paper, we review studies analyzing the prognostic role of EPCs in patients with HF. Through a systematic search, we identified 14 relevant studies. Only one study analyzed mortality as an outcome; the others evaluated the association between EPC levels and patients' characteristics. Overall, results were inconsistent and suggested that levels of EPCs may vary according to factors such as disease severity, underlying cause of cardiomyopathy and medical therapy.

Clinical Evaluation of Root ZX II Electronic Apex Locator in Primary Teeth

European Archives of Paediatric Dentistry : Official Journal of the European Academy of Paediatric Dentistry. Feb, 2012  |  Pubmed ID: 22293103

Aim: To evaluate the accuracy of Root ZX II electronic apex locator (EAL) for root canal working length determination in primary teeth.

Mutations in HpyAVIBM, C(5) Cytosine DNA Methyltransferase from Helicobacter pylori Result in Relaxed Specificity

The FEBS Journal. Jan, 2012  |  Pubmed ID: 22269034

The genome of Helicobacter pylori is rich in restriction-modification (RM) systems. Approximately 4% of the genome codes for components of RM systems. hpyAVIBM, which codes for a phase-variable C(5) cytosine methyltransferase (MTase) from H. pylori, lacks a cognate restriction enzyme. Over-expression of M.HpyAVIB in Escherichia coli enhances the rate of mutations. However, when the catalytically inactive F9N or C82W mutants of M.HpyAVIB were expressed in E. coli, mutations were not observed. The M.HpyAVIB gene itself was mutated to give rise to different variants of the MTase. M.HpyAVIB variants were purified and differences in kinetic properties and specificity were observed. Intriguingly, purified MTase variants showed relaxed substrate specificity. Homologues of hpyAVIBM homologues amplified and sequenced from different clinical isolates showed similar variations in sequence. Thus, hpyAVIBM presents an interesting example of allelic variations in H. pylori where changes in the nucleotide sequence result in proteins with new properties.

In Situ Evidence for Chirality-dependent Growth Rates of Individual Carbon Nanotubes

Nature Materials. 2012  |  Pubmed ID: 22286334

Chiral-selective growth of single-walled carbon nanotubes (SWNTs) remains a great challenge that hinders their use in applications such as electronics and medicine. Recent experimental and theoretical reports have begun to address this problem by suggesting that selectivity may be achieved during nucleation by changing the catalyst composition or structure. Nevertheless, to establish a rational basis for chiral-selective synthesis, the underlying mechanisms governing nucleation, growth, and termination of SWNTs must be better understood. To this end, we report the first measurements of growth rates of individual SWNTs through in situ Raman spectroscopy and correlate them with their chiral angles. Our results show that the growth rates are directly proportional to the chiral angles, in agreement with recent theoretical predictions. Importantly, the evidence singles out the growth stage as responsible for the chiral distribution-distinct from nucleation and termination which might also affect the final product distribution. Our results suggest a route to chiral-selective synthesis of SWNTs through rational synthetic design strategies based on kinetic control.

Positive Pre-resection Pleural Lavage Cytology is Associated with Increased Risk of Lung Cancer Recurrence in Patients Undergoing Surgical Resection: a Meta-analysis of 4450 Patients

Thorax. Jan, 2012  |  Pubmed ID: 22286928

INTRODUCTION: The value of pleural lavage cytology (PLC) in assessing the prognosis of early stage lung cancer is still controversial. No systematic review has investigated the relationship between PLC and lung cancer recurrence. Our primary goal was to investigate the association between positive pre-resection PLC and pleural, distant and overall tumour recurrence in patients undergoing surgical resection. METHODS: Medline, EMBASE and Google Scholar databases were searched up to 2011. All studies reporting relevant outcomes in both patient groups were included. Data were extracted for the following outcomes of interest: overall, local and distant recurrence; and freedom from death (survival-overall and patients with stage I disease only). Random effects meta-analysis was used to aggregate the data. Sensitivity and heterogeneity analysis were performed. RESULTS: A meta-analysis of eight studies at maximum follow-up demonstrated a significant association between positive pre-resection PLC and increased risk of post-resection overall recurrence (OR 4.82, 95% CI 2.45 to 9.51), pleural recurrence (OR 9.89, 95% CI 5.95 to 16.44) and distant cancer recurrence (OR 3.18, 95% CI 1.57 to 6.46). Furthermore, a meta-analysis of 17 studies suggested that positive pre-resection PLC was also associated with unfavourable survival (HR 2.08, 95% CI 1.71 to 2.52). These findings were supported by sensitivity analysis. DISCUSSION: Positive pre-resection PLC is associated with higher overall, distant and local tumour recurrence and unfavourable patient survival outcomes. This technique may therefore act as a predictor of tumour recurrence and adverse survival. Furthermore, its role in including adjuvant chemotherapy to the management protocol should be investigated within randomised controlled trials.

Atorvastatin Delays Progression of Pancreatic Lesions to Carcinoma by Regulating PI3/AKT Signaling in P48(Cre/+) .LSL-Kras(G12D/+) Mice

International Journal of Cancer. Journal International Du Cancer. Jan, 2012  |  Pubmed ID: 22287227

Pancreatic cancer is the one of most common causes of cancer deaths and has the worst prognosis. Clinical observational studies suggest that statins may reduce the risk of pancreatic cancer. The chemopreventive efficacy of the statin atorvastatin (Lipitor®) and the role of the phosphatidyl-inositol 3-kinase(PI3/AKT) signaling pathway were evaluated for the progression of pancreatic intraepithelial neoplasms (PanINs) to pancreatic ductal adenocarcinoma (PDAC) in conditional p48(Cre/+) -LSL-Kras(G12D/+) transgenic mice. Six-week old male p48(Cre/+) -LSL-Kras(G12D/+) (20/group) mice were fed AIN-76A diets containing 0, 200, and 400 ppm atorvastatin for 35 weeks. At termination, pancreata were evaluated histopathologically for PanINs and PDAC, and for various PI3/AKT signaling markers, and inflammatory cytokines, by immunohistochemistry/ immunohistoflourscence, ELISA, Western blotting and/or Reverse Transcription-PCR methods. Control diet-fed mice showed 85% incidence of PDAC; whereas, mice fed with atorvastatin showed PDAC incidence of 65 and 35% respectively (p<0.0001). Similarly, significant suppression of PanIN-3 (22.6%) was observed in mice fed 400 ppm atorvastatin. Importantly, pancreata from atorvastatin-treated mice were 68% free from ductal lesions. Furthermore, pancreas of mice administered with atorvastatin had significantly reduced expressions levels of PCNA, p2X7, p-ERK, RhoA, cyclin D1, survivin, Akt, pAKT, β-catenin, cyclin E, cdK2, and caveolin-1. Also, atorvastatin-treated mice had shown dose-dependent suppression of inflammatory cytokines and a significant increase in tunnel-positive cells, p21 and PARP expression levels in pancreas. Atorvastatin significantly delays the progression of PanIN-1 and -2 lesions to PanIN-3 and PDAC by modulating PI3/AKT signal molecules in a preclinical model, suggesting potential clinical benefits of statins for high risk pancreatic cancer patients. © 2012 Wiley-Liss, Inc.

T(3;8) As the Sole Chromosomal Abnormality in a Myoepithelial Carcinoma Ex Pleomorphic Adenoma: A Putative Progression Event

Head & Neck. Jan, 2012  |  Pubmed ID: 22287457

BACKGROUND: Carcinoma ex pleomorphic adenoma (Ca ex-PA) is defined as a carcinoma arising from a primary (de novo) or recurrent benign pleomorphic adenoma (PA). METHODS: We present a parotid myoepithelial carcinoma ex pleomorphic adenoma in a 38-year-old man with a t(3;8)(p21;q13) as the only chromosomal alteration by cytogenetic and spectral karyotypic analysis (SKY). RESULTS: The finding of this translocation in a subset of PA and in the present case suggests a critical role for this event in the malignant transformation of PA. CONCLUSIONS: Collectively, both the cytogenetic and the molecular studies suggest the concept that PA lacking alterations pursue a benign behavior, whereas those with the t(3;8) translocation may progress to carcinoma. © 2012 Wiley Periodicals, Inc. Head Neck, 2012.

Discovery of a Case of Waugh's Syndrome During a Mission to Haiti

International Journal of Surgery Case Reports. 2012  |  Pubmed ID: 22288034

A rarely reported entity, Waugh's syndrome is the association between intestinal malrotation and intussusception. We present a case of Waugh's syndrome encountered during a medical mission to a resource poor country. PRESENTATION OF CASE: A 3-month-old female presented with septic shock and acute bowel obstruction secondary to intussusception and malrotation. She required aggressive resuscitation and emergent laparotomy, bowel resection, Ladd procedure and temporary ileostomy.

The Case ˆ£ Metabolic Alkalosis in a Patient with Cystic Fibrosis

Kidney International. Feb, 2012  |  Pubmed ID: 22289798

Beneficial Effects of Add-on Raloxifene in Schizophrenia : A Case Report

Archives of Women's Mental Health. Jan, 2012  |  Pubmed ID: 22290018

The role of estrogens in schizophrenia has been proposed from the observation of schizophrenia occurring later and with symptom severity being lesser in women. Utility of estrogens in treatment of psychoses, though seen to be useful, comes with inherent risks of neoplasias, given its agonistic action on breast and endometrium. This risk can be overcome with use of selective estrogen receptor modulators, like raloxifene. Raloxifene has been used in schizophrenia, with improvement in symptoms and cognitive functions. We report the use of raloxifene as an adjunctive treatment, with risperidone, in treatment-resistant form of schizophrenia. The patient, a 29-year-old woman, over a 7-month follow-up period, showed significant improvement in socio-occupational functioning, with reduction in symptom severity.

An Unusual Presentation of Pulmonary Cryptococcosis with Co-existing Disseminated Tuberculosis in an AIDS Patient

Tropical Doctor. Jan, 2012  |  Pubmed ID: 22290112

Although cryptococcosis with lung involvement is not rare in patients with HIV, it is rarely considered in the differential diagnosis of an abnormal chest roentgenogram. Pulmonary cryptococcosis with concomitant opportunistic infections is frequently seen among AIDS and its association with tuberculosis (TB) has been previously reported. Untreated pulmonary cryptococcosis in immunocompromised hosts usually becomes disseminated and results in considerable mortality despite antifungal therapy. We report a case of cryptococcosis with pulmonary involvement in a patient with coexisting disseminated TB in HIV infection.

Early Benefit of Preserved Cognitive Function is Not Sustained at One-year After Cardiac Surgery: a Longitudinal Follow-up of the Randomized Controlled Trial

Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. Jan, 2012  |  Pubmed ID: 22290354

PURPOSE: Recently, we showed that processing of shed blood with a continuous-flow cell saver during cardiopulmonary bypass resulted in a clinically significant reduction in postoperative cognitive decline (POCD) six weeks after coronary artery bypass graft (CABG) surgery. The current study examined if the early benefit of reduced POCD was sustained in the same patient population at one-year follow-up. METHODS: One hundred seventy patients (cell saver group, n = 84; controls, n = 86) underwent neuropsychological testing at baseline and one year after surgery. The raw scores for each test were converted to Z-scores, and a combined Z-score of ten main variables was then calculated for each study group. RESULTS: Postoperative cognitive decline was present in 16 of 84 (19%) patients in the cell saver group (95% confidence interval [CI], 10.8 to 27.2) vs 15 of 86 (17.4%) patients in the control group (95% CI, 9.6 to 25.2) (P = 0.786). Six of the 15 patients in the control group with POCD at six weeks had the impairment at one year and five did not; four were lost to follow-up. Three of the six cell saver patients with POCD at six weeks still had impairment at one year, two did not, and one was not tested. Thirteen (15.4%) and nine (10.5%) patients in the cell saver and control groups, respectively, developed new POCD which was not evident at the six-week follow-up. CONCLUSIONS: The short-term preservation of cognitive function in elderly patients using the cell saver management strategy did not translate into a long-term benefit one year after CABG surgery. The presence of progressing cerebrovascular disease may be responsible for the long-term cognitive decline. (ClinicalTrials.gov number, NCT00193999).

Comparison of ER/PR and HER2 Statuses in Primary and Paired Liver Metastatic Sites of Breast Carcinoma in Patients with or Without Treatment

Journal of Cancer Research and Clinical Oncology. Jan, 2012  |  Pubmed ID: 22290394

PURPOSE: The aim of this study was to determine whether estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor type 2 (HER2) statuses between primary tumors and paired liver metastatic localizations of breast carcinoma were modified by treatment or during the natural metastatic process. METHODS: ER, PR, and HER2 expressions were analyzed on paired tissue specimens taken from the primary and the liver metastatic tumors in breast cancer patients. The first group included 46 women who presented with T1-T4, N0-N3, M0 breast carcinoma when first diagnosed and were treated by neoadjuvant therapy or directly underwent surgery, then received postoperative treatment and developed liver metastasis several months/years later. The second group included 12 patients with liver metastatic breast carcinoma when first diagnosed for breast cancer. HER2 status was determined by immunohistochemistry as well as fluorescence in situ hybridization. RESULTS: Among the 46 patients in the first group, the ER/PR and HER2 statuses (when considered as a whole histological subtype) were changed between primary tumor and liver metastatic lesions in 12 patients (26.1%). While ER and PR status were modified in 14 (30.4%) and 25 (54.3%) patients, respectively, there were only 5 (10.9%) cases showed a discrepancy in the HER2 status. In the second group, the ER/PR and HER2 statuses (when considered as a whole subtype) were consistent between primary and liver metastatic tumor in 10 of 12 (83.3%) patients. ER, PR, and HER2 statuses were modified in 0 of 12 (0%), 4 of 12 (33.3%), and 1 of 12 (8.3%) cases, respectively. CONCLUSIONS: ER/PR and HER2 statuses between primary and liver metastatic lesions of breast carcinoma can be modified after treatment but are stable in most cases during the natural metastatic process.

"Combi-targeting" Mitozolomide: Conferring Novel Signaling Inhibitory Properties to an Abandoned DNA Alkylating Agent in the Treatment of Advanced Prostate Cancer

The Prostate. Jan, 2012  |  Pubmed ID: 22290742

PURPOSE: At the preclinical stage, mitozolomide (MTZ) showed exciting preclinical activity but failed later in clinical trial due to toxic side effects. We surmised that by targeting MTZ to epidermal growth factor receptor (EGFR), we may not only alter its toxicity profile, but also enhance its potency in EGFR-overexpressing tumors. To test this hypothesis, we designed JDF12, studied its mechanism of action in human prostate cancer (PCa) cells and determined its potency in vivo. EXPERIMENTAL DESIGN: To analyze its mixed EGFR-DNA targeting potential, we performed an enzyme linked immunosorbent assay (ELISA) and western blotting analysis of EGFR phosphorylation in cells stimulated with EGF. DNA damage was analyzed using the comet assay, and apoptosis quantitated by annexin V binding assay. Growth inhibition in vitro was determined by the sulforhodamine B (SRB) assay and in vivo efficacy analyzed in male CD-1 nude mice. RESULTS: The results showed that: Under physiological conditions, JDF12 was hydrolyzed to JDF04R and both agents were capable of inhibiting isolated EGFR tyrosine kinase (TK) and EGFR phosphorylation in EGF-stimulated cells. JDF12 significantly damaged DNA, induced apoptosis in DU145 cells and was up to 2-10-fold more potent than equieffective combinations of MTZ and JDF04R or Iressa in a panel that also included LNCaP and its EGFR and ErbB2 transfectants. In vivo, it induced significant antitumor activity in a DU145 xenograft model. CONCLUSIONS: The results suggest that the superior cytotoxicity of JDF12 when compared with MTZ and JDF04R may be imputed to its potent EGFR-DNA targeting properties and confirm the ability of this novel strategy to confer EGFR targeting properties to a classical alkylator. Prostate © 2012 Wiley Periodicals, Inc.

Modern Management of Systolic Anterior Motion of the Mitral Valve

European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery. Jan, 2012  |  Pubmed ID: 22290892

Systolic anterior motion (SAM) of the mitral valve (MV) can be a life-threatening condition. The SAM can result in severe left ventricular outflow tract obstruction and/or mitral regurgitation and is associated with an up to 20% risk of sudden death (which is substantially lower in hypertrophic cardiomyopathy (HCM)). The mechanisms of SAM are complex and depend on the functional status of the ventricle. The SAM can occur in the normal population, but is typically observed in patients with HCM or following MV repair. Echocardiography (2D, 3D and stress) has a central diagnostic role as the application of echocardiographic SAM predictors allows the incorporation of prevention techniques during surgery and post-operative SAM assessment. Cardiac magnetic resonance imaging has a special role in understanding the dynamic nature of SAM, especially in anatomically atypical hearts (including HCM). This article describes what the clinician needs to know about SAM ranging from pathophysiological mechanisms and imaging modalities to conservative (medical) and surgical approaches and their respective outcomes. A stepwise approach is advocated consisting of medical therapy, followed by aggressive volume loading and beta-adrenoceptor blockade. Surgery is the final option. The correct choice of surgical technique requires an understanding of the anatomical substrate of SAM.

Current and Proposed Biomarkers of Anthracycline Cardiotoxicity in Cancer: Emerging Opportunities in Oxidative Damage and Autophagy

Current Molecular Medicine. Jan, 2012  |  Pubmed ID: 22292442

A biomarker is defined as "a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or biological responses to a therapeutic intervention." Biomarkers can be utilized to detect disease, evaluate treatment risks, or determine treatment effectiveness. In the case of cancer, anthracyclines such as doxorubicin are front-line therapy to treat a number of different malignancies including breast cancer. However, a significant fraction of patients experience drug-induced cardiotoxicity. This toxicity is dose-limiting and can cause long-term morbidity or mortality. There is an unmet medical need to identify patients who are at risk for doxorubicin-induced cardiotoxicity, to detect cardiac damage early so that patient risk can be minimized, and to monitor the success of cardioprotective strategies. Therefore, doxorubicin treatment of cancer is an excellent example of the need for biomarkers to indicate drug safety in addition to drug efficacy. In this review we will discuss the mechanism of doxorubicin-associated cardiotoxicity, as well as other cancer therapies that induce cardiac toxicity by causing oxidative damage. We will also evaluate established and proposed biomarkers for cardiotoxicity based on our evolving knowledge of oxidative damage and subsequent autophagy. Finally, we will discuss advantages of combining oxidative damage- and autophagy-based protein biomarkers with current biomarkers such as troponins to facilitate early detection and mitigation of cardiotoxicity induced by cancer therapeutic agents.

Lower Rim 1,3-Di{4-antipyrine}amide Conjugate of Calix[4]arene: Synthesis, Characterization, and Selective Recognition of Hg(2+)and Its Sensitivity Toward Pyrimidine Bases

The Journal of Organic Chemistry. Feb, 2012  |  Pubmed ID: 22263565

The structurally characterized lower rim 1,3-di{4-antipyrine}amide conjugate of calix[4]arene (L) exhibits high selectivity toward Hg(2+) among other biologically important metal ions, viz., Na(+), K(+), Ca(2+), Mg(2+), Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+), Pb(2+), and Ag(+) as studied by fluorescence, absorption, and ESI MS. L acts as a sensor for Hg(2+) by switch-off fluorescence and exhibits a lowest detectable concentration of 1.87 ± 0.1 ppm. The complex formed between L and Hg(2+) is found to be 1:1 on the basis of absorption and fluorescence titrations and was confirmed by ESI MS. The coordination features of the mercury complex of L were derived on the basis of DFT computations and found that the Hg(2+) is bound through an N(2)O(2) extending from both the arms to result in a distorted octahedral geometry with two vacant sites. The nanostructural features such as shape and size obtained using AFM and TEM distinguishes L from its Hg(2+) complex and were different from those of the simple mercuric perchlorate. L is also suited to sense pyrimidine bases by fluorescence quenching with a minimum detection limit of 1.15 ± 0.1 ppm in the case of cytosine. The nature of interaction of pyrimidine bases with L has been further studied by DFT computational calculations and found to have interactions through a hydrogen bonding and NH-π interaction between the host and the guest.

The V-ATPase As a Target for Antifungal Drugs

Current Protein & Peptide Science. Jan, 2012  |  Pubmed ID: 22264127

The ubiquitous and essential V-ATPase is a worthy chemotherapeutic target in the escalating battle against invasive fungal infections. Pathogenic fungi require optimum V-ATPase function for secretion of virulence factors, induction of stress response pathways, hyphal morphology and homeostasis of pH and other cations in order to successfully survive within and colonize the host. This review discusses why impairment of V-ATPase activity confers multidrug sensitivity and loss of virulence. Recent evidence points to the V-ATPase as a novel downstream target of the azole class of antifungals that inhibit the biogenesis of ergosterol. Depletion of ergosterol from vacuolar membranes led to progressive alkalization of yeast vacuoles, loss of V-ATPase activity and growth inhibition that could be rescued by exogenous ergosterol feeding. Other studies point to a critical role for sphingolipids, phospholipids and cardiolipin in V-ATPase function. Thus, drugs that inhibit the V-ATPase directly, or indirectly by modulating the membrane milieu, can profoundly affect fungal viability and virulence. These findings justify a systematic screen for fungal specific V-ATPase inhibitors or membrane active compounds that can be used in antifungal chemotherapy.

"Local Drug Delivery of Alendronate Gel for the Treatment of Chronic Periodontitis Subjects With Diabetes Mellitus : A Double Masked Controlled Clinical Trial"

Journal of Periodontology. Jan, 2012  |  Pubmed ID: 22264208

Background: Alendronate (ALN), increases alveolar bone density with systemic use and on local delivery into the periodontal pocket, it has been found to increase bone formation. The purpose of the present study was to explore the efficacy of 1% ALN gel as local drug delivery system in adjunct to scaling and root planing (SRP) for the treatment of intrabony defects in chronic periodontitis subjects with type 2 diabetes as compared to a placebo gel. Material and Methods: 70 intrabony defects were treated either with 1% ALN gel or placebo gel. Clinical parameters were recorded at baseline, 2 month and 6 month while radiographic parameters were recorded at baseline and 6 month. Defect fill at baseline and at 6 month was calculated on standardized radiographs by using the image analysis software. Results: Mean probing depth reduction and mean periodontal attachment level gain was found to greater in ALN group than placebo group, both at 2 month and at 6 month. Furthermore, significantly greater mean percentage of bone fill was found in the ALN group (44.2 ± 11.78%) compared to placebo group (2.8 ± 1.61%). Conclusions: In type 2 diabetic subjects it was found that local delivery of 1% ALN into periodontal pocket resulted in a significant increase in the probing depth reduction, periodontal attachment level gain, and improved bone fill as compared to placebo gel as an adjunct to SRP. Thus ALN can be used as an adjunct to SRP to provide a new dimension in the periodontal therapy in the near future.

Treatment of Lepromatous Ulcers Using Citric Acid As a Sole Antimicrobial Agent

International Wound Journal. Jan, 2012  |  Pubmed ID: 22264346

A prospective study was carried out to assess the role of citric acid as a sole antimicrobial agent in the management of lepromatous ulcers. Thirty-four known cases of lepromatous ulcers not responding to conventional antibiotic therapies for long duration were investigated for culture and susceptibility studies. Staphylococcus aureus (25·00%) and Klebsiella spp. (23·43%) were found to be the most common isolates. Amikacin (68·75%) and ciprofloxacin (67·18%) were found to be the most effective antimicrobial agents. Topical application of citric acid ointment resulted in complete healing in 25 (73·52%) cases. In eight cases (26·48%), there was elimination of infective agent from ulcer site and formation of healthy granulation, but no complete healing of ulcer was seen. Results indicate that citric acid is the best alternative for the effective management of lepromatous ulcers when other therapies are exhausted.

Blindness and Long-term Progression of Visual Field Defects in Chinese Patients with Primary Angle-closure Glaucoma

American Journal of Ophthalmology. Feb, 2012  |  Pubmed ID: 22264951

Priority Symptoms in Advanced Breast Cancer: Development and Initial Validation of the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (NFBSI-16)

Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research. Jan, 2012  |  Pubmed ID: 22264987

By using methods consistent with recent regulatory guidance on patient-reported outcomes as endpoints in clinical trials, we created a new version of the Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (FBSI), with emphasis on patient input during the development process.

Exogenous Mineralization of Cell-seeded and Unseeded Collagen-chitosan Hydrogels Using Modified Culture Medium

Acta Biomaterialia. Apr, 2012  |  Pubmed ID: 22266029

Induced biomineralization of materials has been employed as a strategy to increase integration with host tissue, and more recently as a method to control cell function in tissue engineering. However, mineralization is typically performed in the absence of cells, since hypertonic solutions that lack the nutrients and culture components required for the maintenance of cell viability are often used. In the present study, we exposed fibroblast-seeded three-dimensional collagen-chitosan hydrogels to a defined culture medium modified to have specific concentrations of ions involved in biomineralization. The modified medium caused a significant increase in calcium deposition in collagen-chitosan gels, relative to constructs incubated in a standard medium, though serum supplementation attenuated mineral deposition. Collagen-chitosan constructs became opaque over 3days of mineralization in modified Dulbecco's modified Eagle medium (DMEM), in contrast to translucent control gels incubated in standard DMEM. Histological staining confirmed increased levels of mineral in the treated constructs. Rheological characterization showed that both the storage and loss moduli increased significantly in mineralized materials. Mineralization of fibroblast-seeded constructs resulted in decreased cell viability and proliferation rate over 3days of incubation in modified medium, but the cell population remained over 75% viable and regained its proliferative potential after rescue in standard culture medium. The ability to mineralize protein matrices in the presence of cells could be useful in creating mechanically stable tissue constructs, as well as to study the effects of the tissue microenvironment on cell function.

Age-dependent Decline of DNA Base Excision Repair Activity in Rat Cortical Neurons

Mechanisms of Ageing and Development. Jan, 2012  |  Pubmed ID: 22266244

Synthetic oligonucleotide duplexes containing a single uracil (U) or 8-oxoguanine (8-oxoG) were used as a model substrates to assess the base excision repair (BER) ability of neuronal extracts prepared from the cerebral cortex of young (7 days), adult (180days) and old (720days) rats. Our results demonstrate that BER activity in neurons markedly declines with age. The decline in BER could be attributed to decrease in the expression levels and activities of BER enzymes. Supplementing neuronal extracts with uracil DNA-glycosylase (UDG), 8-oxoguanine DNA glycosylase (OGG1), apurinic endonuclease 1, pol β and T(4) DNA ligase independently could not restore the loss of BER activity in adult and old neuronal extracts. However, supplementation of pol β in combination of T(4) DNA ligase to neuronal extract, improved the BER in adult and old neuronal extracts. Additional supplementation of the extracts with UDG or OGG1 apart from pol β and T(4) DNA ligase, or with all pure enzymes restored very markedly the loss of BER in aging neurons. These results suggest the age-dependent decline in BER is due to an overall deficiency of the various factors needed for BER but pol β and DNA ligase seem to be the most limiting factors.

Effect of Spectrum Bias on the Diagnostic Accuracy of Spectral Domain Optical Coherence Tomograph in Glaucoma

Investigative Ophthalmology & Visual Science. Jan, 2012  |  Pubmed ID: 22266520

Purpose:To evaluate the influence of control group on the diagnostic accuracy of spectral domain optical coherence tomograph (SDOCT) in early glaucoma.Methods:In a diagnostic, case-control study, 119 eyes of 60 normal subjects with no suspicious findings of glaucoma (control cohort 1), 76 eyes of 41 subjects referred by general ophthalmologists as glaucoma suspects based on optic disc morphology, but found by glaucoma experts to be normal with physiological variations of optic nerves (control cohort 2) and 65 eyes of 46 early glaucoma patients (cases) underwent optic nerve head (ONH), retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) imaging with the commercially available SDOCT.Results:Areas under the receiver operating characteristic curves (AUC) of ONH parameters to discriminate glaucomatous eyes from normal eyes of control cohort 2 were significantly lesser (p<0.001) than those to discriminate glaucomatous eyes from normal eyes of control cohort 1. AUCs of RNFL parameters to discriminate glaucomatous eyes from normal eyes of control cohort 2 and 1 were comparable. Though the AUCs of GCC thickness parameters were comparable, AUCs of GCC focal and global loss volume with control cohort 2 (0.684 and 0.671 respectively) were significantly lesser (p<0.05) than with control cohort 1 (0.881 and 0.841 respectively).Conclusions:Abilities of most SDOCT parameters in detecting glaucoma significantly decreased when evaluated against a clinically relevant, control group with suspicious looking optic nerves compared to that against a control group consisting of normal subjects with no suspicious findings of glaucoma.

Epitope-tagged Dopamine Transporter Knock-in Mice Reveal Rapid Endocytic Trafficking and Filopodia Targeting of the Transporter in Dopaminergic Axons

The FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology. Jan, 2012  |  Pubmed ID: 22267337

The plasma membrane dopamine (DA) transporter (DAT) is essential for reuptake of extracellular DA. DAT function in heterologous cells is regulated by subcellular targeting, endocytosis, and intracellular trafficking, but the mechanisms regulating neuronal DAT remain poorly understood. Hence, we generated a knock-in mouse expressing a hemagglutinin (HA)-epitope-tagged DAT to study endogenous transporter trafficking. Introduction of the HA tag into the second extracellular loop of mouse DAT did not perturb its expression level, distribution pattern, or substrate uptake kinetics. Live-cell fluorescence microscopy imaging using fluorescently labeled HA-specific antibody and a quantitative HA-antibody endocytosis assay demonstrated that in axons HA-DAT was primarily located in the plasma membrane and internalized mostly in growth cones and varicosities, where synaptic vesicle markers were also concentrated. Formation of varicosities was frequently preceded or accompanied by highly dynamic filopodia-like membrane protrusions. Remarkably, HA-DAT often concentrated at the tips of these filopodia. This pool of HA-DATs exhibited low lateral membrane mobility. Thus, DAT-containing filopodia may be involved in synaptogenesis in developing DA neurons. Treatment of neurons with amphetamine increased mobility of filopodial HA-DAT and accelerated HA-DAT endocytosis in axons, suggesting that chronic amphetamine may interfere with DA synapse development. Interestingly, phorbol esters did not accelerate endocytosis of axonal DAT.-Rao, A., Richards, T. L., Simmons, D., Zahniser, N. R., Sorkin, A. Epitope-tagged dopamine transporter knock-in mice reveal rapid endocytic trafficking and filopodia targeting of the transporter in dopaminergic axons.

Development of a Mesoamerican Intra-genepool Genetic Map for Quantitative Trait Loci Detection in a Drought Tolerant × Susceptible Common Bean (Phaseolus Vulgaris L.) Cross

Molecular Breeding : New Strategies in Plant Improvement. Jan, 2012  |  Pubmed ID: 22267950

Drought is a major constraint to common bean (Phaseolus vulgaris L.) production, especially in developing countries where irrigation for the crop is infrequent. The Mesoamerican genepool is the most widely grown subdivision of common beans that include small red, small cream and black seeded varieties. The objective of this study was to develop a reliable genetic map for a Mesoamerican × Mesoamerican drought tolerant × susceptible cross and to use this map to analyze the inheritance of yield traits under drought and fully irrigated conditions over 3 years of experiments. The source of drought tolerance used in the cross was the cream-seeded advanced line BAT477 crossed with the small red variety DOR364 and the population was made up of recombinant inbred lines in the F5 generation. Quantitative trait loci were detected by composite interval mapping for the traits of overall seed yield, yield per day, 100 seed weight, days to flowering and days to maturity for each field environment consisting of two treatments (irrigated and rainfed) and lattice design experiments with three repetitions for a total of six environments. The genetic map based on amplified fragment length polymorphism and random amplified polymorphic DNA markers was anchored with 60 simple sequence repeat (SSR) markers and had a total map length of 1,087.5 cM across 11 linkage groups covering the whole common bean genome with saturation of one marker every 5.9 cM. Gaps for the genetic map existed on linkage groups b03, b09 and b11 but overall there were only nine gaps larger than 15 cM. All traits were inherited quantitatively, with the greatest number for seed weight followed by yield per day, yield per se, days to flowering and days to maturity. The relevance of these results for breeding common beans is discussed in particular in the light of crop improvement for drought tolerance in the Mesoamerican genepool.

Correction: Increased Neuroinflammatory and Arachidonic Acid Cascade Markers, and Reduced Synaptic Proteins, in Brain of HIV-1 Transgenic Rats

Journal of Neuroinflammation. Jan, 2012  |  Pubmed ID: 22269462

ABSTRACT: Correction to Rao J S, Kim H W, Kellom M, Greenstein D, Chen M, Kraft A D, Harry G J, Rapoport S I, Basselin M. Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats. Journal of Neuroinflammation 8:101.

Clinical, Molecular, and Genetic Correlates of Lymphatic Spread in Clear Cell Renal Cell Carcinoma

European Urology. Jan, 2012  |  Pubmed ID: 22269604

BACKGROUND: While it is well known that clear cell renal cell carcinoma (ccRCC) that presents with lymphatic spread is associated with an extremely poor prognosis, its molecular and genetic biology is poorly understood. OBJECTIVE: Define the clinicopathologic, molecular, and genetic biological characteristics of these tumors in comparison to nonmetastatic (N0M0) renal cell carcinomas. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study defined clinicopathologic features, expression of 28 molecular markers, and occurrence of chromosomal aberrations for their correlation with lymphatic spread in three cohorts of 502, 196, and 272 patients, respectively. MEASUREMENTS: Fisher exact test or the χ(2) test were used to compare categorical variables; continuous variables were compared with the Mann-Whitney U test or student t test. Cut-off values were calculated based on receiver operating characteristic curves and the Youden Index. Uni- and multivariate regression analyses were used to investigate the correlation with lymphatic spread. RESULTS AND LIMITATIONS: In clinical analyses, a predictive model consisting of smoking history (p=0.040), T stage (p<0.0001), Fuhrman grade (p<0.0001), Eastern Cooperative Oncology Group performance status (p<0.0001), and microvascular invasion (p<0.0001) was independently associated with lymphatic spread. After adjustment with these clinical variables, low carbonic anhydrase IX (CAIX) (p=0.043) and high epithelial vascular endothelial growth factor receptor 2 (p=0.033) protein expression were associated with a higher risk of lymphatic spread, and loss of chromosome 3p (p<0.0001) with a lower risk. The current study is limited by its retrospective design, small sample size, and single-center experience. CONCLUSIONS: The low rates of CAIX expression and loss of chromosome 3p suggest that lymphatic spread in ccRCC occurs independently of von Hippel-Lindau tumor suppressor inactivation.

HspB2/myotonic Dystrophy Protein Kinase Binding Protein (MKBP) As a Novel Molecular Chaperone: Structural and Functional Aspects

PloS One. 2012  |  Pubmed ID: 22272249

The small heat shock protein, human HspB2, also known as Myotonic Dystrophy Kinase Binding Protein (MKBP), specifically associates with and activates Myotonic Dystrophy Protein Kinase (DMPK), a serine/threonine protein kinase that plays an important role in maintaining muscle structure and function. The structure and function of HspB2 are not well understood. We have cloned and expressed the protein in E.coli and purified it to homogeneity. Far-UV circular dichroic spectrum of the recombinant HspB2 shows a β-sheet structure. Fluorescence spectroscopic studies show that the sole tryptophan residue at the 130(th) position is almost completely solvent-exposed. Bis-ANS binding shows that though HspB2 exhibits accessible hydrophobic surfaces, it is significantly less than that exhibited by another well characterized small HSP, αB-crystallin. Sedimentation velocity measurements show that the protein exhibits concentration-dependent oligomerization. Fluorescence resonance energy transfer study shows that HspB2 oligomers exchange subunits. Interestingly, HspB2 exhibits target protein-dependent chaperone-like activity: it exhibits significant chaperone-like activity towards dithiothreitol (DTT)-induced aggregation of insulin and heat-induced aggregation of alcohol dehydrogenase, but only partially prevents the heat-induced aggregation of citrate synthase, co-precipitating with the target protein. It also significantly prevents the ordered amyloid fibril formation of α-synuclein. Thus, our study, for the first time, provides biophysical characterization on the structural aspects of HspB2, and shows that it exhibits target protein-dependent chaperone-like activity.

Are Tuberculosis Patients in a Tertiary Care Hospital in Hyderabad, India Being Managed According to National Guidelines?

PloS One. 2012  |  Pubmed ID: 22272323

A tertiary health care facility (Government General and Chest hospital) in Hyderabad, India.

A Multicenter Evaluation of Diagnostic Tools to Define Endpoints for Programs to Eliminate Bancroftian Filariasis

PLoS Neglected Tropical Diseases. Jan, 2012  |  Pubmed ID: 22272369

Successful mass drug administration (MDA) campaigns have brought several countries near the point of Lymphatic Filariasis (LF) elimination. A diagnostic tool is needed to determine when the prevalence levels have decreased to a point that MDA campaigns can be discontinued without the threat of recrudescence. A six-country study was conducted assessing the performance of seven diagnostic tests, including tests for microfilariae (blood smear, PCR), parasite antigen (ICT, Og4C3) and antifilarial antibody (Bm14, PanLF, Urine SXP). One community survey and one school survey were performed in each country. A total of 8,513 people from the six countries participated in the study, 6,443 through community surveys and 2,070 through school surveys. Specimens from these participants were used to conduct 49,585 diagnostic tests. Each test was seen to have both positive and negative attributes, but overall, the ICT test was found to be 76% sensitive at detecting microfilaremia and 93% specific at identifying individuals negative for both microfilariae and antifilarial antibody; the Og4C3 test was 87% sensitive and 95% specific. We conclude, however, that the ICT should be the primary tool recommended for decision-making about stopping MDAs. As a point-of-care diagnostic, the ICT is relatively inexpensive, requires no laboratory equipment, has satisfactory sensitivity and specificity and can be processed in 10 minutes-qualities consistent with programmatic use. Og4C3 provides a satisfactory laboratory-based diagnostic alternative.

Lifestyle and Genetic Contributions to Cognitive Decline and Hippocampal Structure and Function in Healthy Aging

Current Alzheimer Research. Jan, 2012  |  Pubmed ID: 22272622

Background: Engagement in cognitively stimulating activities (CA) and leisure time physical activity (PA) have been associated with maintaining cognitive performance and reducing the likelihood of cognitive decline in older adults. However, neural mechanisms underlying protective effects of these lifestyle behaviors are largely unknown. In the current study, we investigated the effect of self-reported PA and CA on hippocampal volume and semantic processing activation during a fame discrimination task, as measured by functional magnetic resonance imaging (fMRI). We also examined whether possession of the apolipoprotein E (APOE) ε4 allele could moderate the effect of PA or CA on hippocampal structure or function. METHODS: Seventy-eight healthy, cognitively intact older adults underwent baseline neuropsychological assessment, hippocampal volume measurement via manually-traced structural MRI, and task-activated fMRI. RESULTS: After 18 months, 27 participants declined by one standard deviation or more on follow-up neuropsychological testing. Logistic regression analyses revealed that CA alone or in combination with baseline hippocampal structure or functional activity did not predict the probability of cognitive decline. In contrast, PA interacted with APOE ε4 status such that engagement in PA reduced the risk of cognitive decline in APOE ε4 carriers only. Furthermore, the benefits of PA appeared to diminish with reduced functional activity or volume in the hippocampus. CONCLUSIONS: Our findings suggest that increased leisure time PA is associated with reduced probability of cognitive decline in persons who are at high risk for AD. The beneficial effects of PA in this group may be related to enhancement of the functional and structural integrity of the hippocampus.

Rhodium-Catalyzed Xanthone Formation from 2-Aryloxybenzaldehydes Via Cross-Dehydrogenative Coupling (CDC)

Organic Letters. Feb, 2012  |  Pubmed ID: 22272652

A concise and straightforward strategy to construct a xanthone skeleton via an intramolecular cross-dehydrogenative coupling (CDC) of 2-aryloxybenzaldehydes has been developed. The reaction proceeded smoothly without any need of preactivation of the aldehyde group. It can tolerate various functional groups and provides an applicable protocol to construct a wide range of xanthone derivatives.

Evaluation of the Coagulation Profile Among Oral and Vaginal Combined Hormonal Contraceptive Users Using Sonoclot Coagulation Analyzer

Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. Jan, 2012  |  Pubmed ID: 22275394

Combined hormonal contraceptives possess an inherent risk of thrombus-related events. The purpose of this study is to elucidate alterations in the coagulation profile among young women using combined oral contraceptive (COC) or combined vaginal contraceptive (CVC) compared to a normal, healthy, female control group using the Sonoclot coagulation analyzer. We enrolled 159 participants (64 control individuals, 51 COC users, and 44 CVC users). Each participant completed a survey of medical history, family medical history, and lifestyle choices. Citrated venous whole blood was collected and analyzed using the Sonoclot coagulation analyzer. After adjusting for age, race, alcohol consumption, sleeping habits, and family history of cardiovascular disease, and stroke, we observed COC and CVC users had mostly similar coagulation profiles except when compared to the control, and COC and CVC users had an elevated glass bead peak signal while COC users had a shorter peak time.

Prevalence of Uncorrected Refractive Errors, Presbyopia and Spectacle Coverage in Marine Fishing Communities in South India: Rapid Assessment of Visual Impairment (RAVI) Project

Ophthalmic & Physiological Optics : the Journal of the British College of Ophthalmic Opticians (Optometrists). Mar, 2012  |  Pubmed ID: 22276902

Citation information: Marmamula S, Madala SR & Rao GN. Prevalence of uncorrected refractive errors, presbyopia and spectacle coverage in marine fishing communities in South India: Rapid Assessment of Visual Impairment (RAVI) project. Ophthalmic Physiol Opt 2012, 32, 149-155. doi: 10.1111/j.1475-1313.2012.00893.x ABSTRACT: Purpose:  To investigate the prevalence of uncorrected refractive errors, presbyopia and spectacle coverage in subjects aged 40 years or more using a novel Rapid Assessment of Visual Impairment (RAVI) methodology. Methods:  A population-based cross-sectional study was conducted using cluster random sampling to enumerate 1700 subjects from 34 clusters predominantly inhabited by marine fishing communities in the Prakasam district of Andhra Pradesh, India. Unaided, aided and pinhole visual acuity (VA) was assessed using a Snellen chart at a distance of 6 m. Near vision was assessed using an N notation chart. Uncorrected refractive error was defined as presenting VA < 6/18 and improving to ≥6/18 with pinhole. Uncorrected presbyopia was defined as binocular near vision worse than N8 in subjects with binocular distance VA ≥ 6/18. Results:  1560 subjects (response rate - 92%) were available for examination. Of these, 54.6% were female and 10.1% were ≥70 years of age. Refractive error was present in 250 individuals. It was uncorrected in 179 (unmet need) and corrected in 71 (met need) individuals. Among 1094 individuals with no distance visual impairment, presbyopia was present in 494 individuals. It was uncorrected in 439 (unmet need) and corrected in 55 individuals (met need). Spectacle coverage was 28.4% for refractive errors and 11.1% for presbyopia. Conclusions:  There is a high unmet need for uncorrected refractive errors and presbyopia among marine fishing communities in the Prakasam district of South India. The data from this study can now be used as a baseline prior to the commencement of eye care services in this region.

Comment on the Article "Proposed Clinical Classification for Oral Submucous Fibrosis" by Chandramani B. More Et Al

Oral Oncology. Mar, 2012  |  Pubmed ID: 22277576

Impact of Anemia on Platelet Response to Clopidogrel in Patients Undergoing Percutaneous Coronary Stenting

The American Journal of Cardiology. Jan, 2012  |  Pubmed ID: 22277895

High residual platelet reactivity (HRPR) on clopidogrel is a predictor of recurrent ischemic events in patients undergoing percutaneous coronary interventions (PCI). Significant intraindividual variability in platelet aggregation on repeat testing has been reported. To understand factors contributing to the variability in platelet aggregation testing, we examined clinical and laboratory elements linked to HRPR in 255 consecutive patients tested ≥12 hours after PCI using light transmission aggregometry (LTA) in response to adenosine diphosphate 5 μmol/L and VerifyNow P2Y12 assay (VNP2Y12; Accumetrics). HRPR was defined as >46% residual aggregation for LTA and >236 P2Y12 response units (PRUs) for VNP2Y12. On multivariate analysis the only variable independently associated with HRPR with both LTA and VNP2Y12 was laboratory-defined anemia. Prevalences of HRPR by LTA were 34.3% in anemic patients, 15.6% in patients with normal hemoglobin levels, and 59.8% versus 25.9% by VNP2Y12 (p <0.005 for the 2 comparisons). In a subgroup of 50 patients, testing was done before and after the clopidogrel loading dose. At baseline there were no differences in platelet aggregation with either assay; however, absolute decrease in reactivity after the clopidogrel load was significantly less in anemic patients compared to patients with normal hemoglobin (change in residual aggregation by LTA 15.8 ± 5.8% vs 28.8 ± 3.2%, p <0.05; change in PRU by VNP2Y12 56.5 ± 35.5 vs 145.0 ± 14.2 PRUs, p <0.05, respectively). In conclusion, anemia is an important contributor to apparent HRPR on clopidogrel and may explain some of the intraindividual variability of platelet aggregation testing.

Determination of the Plasma Pharmacokinetic and Tissue Distributions of Swertiamarin in Rats by Liquid Chromatography with Tandem Mass Spectrometry

Arzneimittel-Forschung. Jan, 2012  |  Pubmed ID: 22278630

An LC-MS/MS method was developed for the quantification of swertiamarin (CAS 17388-39-5) in rat plasma and tissues using gentiopicroside as the internal standard (IS). Swertiamarin and an IS were extracted from plasma and tissues by a simple solid-phase extraction (SPE) procedure. Separation was achieved on a Phenomenex kinetex-C18 column (100 mm×2.1 mm, 2.6 µm) with an isocratic mobile phase consisting of methanol and water (22:78, v/v) with 0.1% acetic acid at a flow rate of 0.2 mL/min. The analyte and IS were detected by negative ion electrospray ionisation in multiple-reaction monitoring mode while monitoring the transitions of m/z 433 [M + CH3COO] - →179 and m/z 415 [M + CH3COO] - →179 for swertiamarin and the IS, respectively. The method was validated with respect to selectivity, matrix effect, linearity, accuracy, precision, recovery and stability. The method was successfully applied in a pharmacokinetic study of swertiamarin after intravenous and oral administration to rats. The pharmacokinetics of swertiamarin showed rapid absorption and elimination, and its absolute bioavailability was low at 10.3%. After oral administration to rats, swertiamarin was rapidly and widely distributed in its tissues. High concentrations were found in the liver and kidney, indicating that swertiamarin was possibly absorbed in the liver and eliminated by the kidney.

Transplantation of Human Embryonic Stem Cells Onto a Partially Wounded Human Cornea in Vitro

Acta Ophthalmologica. Jan, 2012  |  Pubmed ID: 22280565

Purpose:  The aim of this study was to investigate whether cells originating from human embryonic stem cells (hESCs) could be successfully transplanted onto a partially wounded human cornea. A second aim was to study the ability of the transplanted cells to differentiate into corneal epithelial-like cells. Methods:  Spontaneously, differentiated hESCs were transplanted onto a human corneal button (without limbus) with the epithelial layer partially removed. The cells were cultured on Bowman's membrane for up to 9 days, and the culture dynamics documented in a time-lapse system. As the transplanted cells originated from a genetically engineered hESC line, they all expressed green fluorescent protein, which facilitated their identification during the culture experiments, tissue preparation and analysis. To detect any differentiation into human corneal epithelial-like cells, we analysed the transplanted cells by immunohistochemistry using antibodies specific for CK3, CK15 and PAX6. Results:  The transplanted cells established and expanded on Bowman's membrane, forming a 1-4 cell layer surrounded by host corneal epithelial cells. Expression of the corneal marker PAX6 appeared 3 days after transplantation, and after 6 days, the cells were expressing both PAX6 and CK3. Conclusion:  This shows that it is possible to transplant cells originating from hESCs onto Bowman's membrane with the epithelial layer partially removed and to get these cells to establish, grow and differentiate into corneal epithelial-like cells in vitro.

Effect of Vitrification on Meiotic Maturation and Expression of Genes in Immature Goat Cumulus Oocyte Complexes

Cryobiology. Jan, 2012  |  Pubmed ID: 22280956

The aim of the study was to evaluate meiotic maturation, and expression of genes coding for oocyte secreted factors (GDF9, BMP15, TGFBR1, and BPR2) and apoptosis (BCL2, BAX and P53) after vitrification of immature goat cumulus oocyte complexes (COCs) and in vitro maturation. COCs were vitrified in a solution containing ethylene glycol, dimethyl sulfoxide and sucrose using either a conventional straw (CS), open pulled straw (OPS), cryoloop (CL), hemistraw (HS) or cryotop (CT). Freshly collected COCs (Control), COCs exposed to vitrification and dilution solutions without cryopreservation (EC) and vitrified-warmed COCs were matured in vitro for 27h. The viability of vitrified-warmed COCs 2h post warming and in vitro maturation was similar for CL, HS and CT. The proportion of oocytes that extruded a 1st polar body and reached TI/MII was significantly higher with CT and HS followed by CL, OPS and CS. Gene expression of GDF9, BMP15, BMPR2, BAX and P53 were comparable to control levels for OPS, CL, HS and CT. The gene expression pattern in CS vitrified COCs was by contrast changed in that GDF9, BMP15, TGFBR1 and BAX were up regulated and BMPR2, BCL2 and P53 down regulated. In conclusion immature goat COCs vitrified using CT and HS showed that viability, maturation rates and expression of genes coding for oocyte secreted factors and apoptosis were similar to non-vitrified controls.

Neutrophil Lymphocyte Ratio As a Measure of Systemic Inflammation in Prevalent Chronic Diseases in Asian Population

International Archives of Medicine. 2012  |  Pubmed ID: 22281066

ABSTRACT: