Protocols and Video Articles Authored by Heeral J. Sheth

Plug the Lung Until It Grows, a New Method to Treat Congenital Diaphragmatic Hernia in Utero Pediatric Surgery International. Jun, 1996 | Pubmed ID: 24057746

TAPS Procedure for Correcting Ventral Chordee Pediatric Surgery International. Jun, 1996 | Pubmed ID: 24057749

The Design and Screening of Drugs to Prevent Acquired Sensorineural Hearing Loss Expert Opinion on Drug Discovery. May, 2011 | Pubmed ID: 22646075 Introduction: Sensorineural hearing loss affects a high percentage of the population. Ototoxicity is a serious and pervasive problem in patients treated with cisplatin. Strategies to ameliorate ototoxicity without compromising on antitumor activity of treatments are urgently needed. Similar problems occur with aminoglycoside antibiotic therapy for infections. Noise-induced hearing loss affects a large number of people. The use of ear protection is not always possible or effective. The prevention of hearing loss with drug therapy would have a huge impact in reducing the number of people with hearing loss from these major causes. Areas covered: This review discusses significant research findings dealing with the use of protective agents against hearing loss caused by cisplatin, aminoglycoside antibiotics and noise trauma. The efficacy in animal studies and the application of these protective agents in clinical trials that are ongoing are presented. Expert opinion: The reader will gain new insights into current and projected future strategies to prevent sensorineural hearing loss from cisplatin chemotherapy, aminoglycoside antibiotic therapy and noise exposure. The future appears to offer numerous agents to prevent hearing loss caused by cisplatin, aminoglycoside antibiotics and noise. Novel delivery systems will provide ways to guide these protective agents to the desired target areas in the inner ear and circumvent problems with therapeutic interference of antitumor and antibiotics agents as well as minimize undesired side effects.

Antiobesity Effect of Stellaria Media Against Drug Induced Obesity in Swiss Albino Mice Ayu. Oct, 2011 | Pubmed ID: 22661858 The whole plant of Stellaria media (family: Caryophyllaceae) has been tested for its antiobesity activity by using progesterone-induced obesity model in female albino mice. The effect of S. media on food consumption pattern, change in body weight, thermogenesis, lipid metabolism, and histology of fat pad. were examined. Methanolic and alcoholic extracts of the S. media were used in the study. Methanolic extract of S. media (MESM) have prevented the increase in body weight, adipose tissue weight and size, and upturned obesity and associated complications. MESM has also shown promising effects compared with alcoholic extract of S. media may be because of its multiple mechanisms. These findings suggest that antiobesity activity produced by MESM is because of its anorexic property mediated by saponin and flavonoid and partly of by its Î²-sitosterol content. Î²-Sitosterol in the plant extract was confirmed by thin-layer chromatography study. Î²-sitosterol is plant sterol having structural similarity with dietary fat which do the physical competition in the gastrointestinal tract and reduces fat absorption. Before carrying in vivo activity detail pharmacognostic and phytochemical analysis of the extracts was carried out. The plant has shown the presence of saponin, flavonoids, steroids and triterpenoids, glycosides, and anthocynidine. By this study, it can be concluded that, MESM is beneficial in suppression of obesity induced by progesterone.

Post Tenectplase Angioplasty Vs PAMI in ST Elevation MI. (Pathak Trial) Indian Heart Journal. May-Jun, 2011 | Pubmed ID: 22734344

Neurocritical Care Education During Neurology Residency: AAN Survey of US Program Directors Neurology. May, 2012 | Pubmed ID: 22573636 Limited information is available regarding the current state of neurocritical care education for neurology residents. The goal of our survey was to assess the need and current state of neurocritical care training for neurology residents.

Activation of Toll-like Receptor 4 is Necessary for Trauma Hemorrhagic Shock-induced Gut Injury and Polymorphonuclear Neutrophil Priming Shock (Augusta, Ga.). Jul, 2012 | Pubmed ID: 22575992 Interactions of toll-like receptors (TLRs) with nonmicrobial factors play a major role in the pathogenesis of early trauma-hemorrhagic shock (T/HS)-induced organ injury and inflammation. Thus, we tested the hypothesis that TLR4 mutant (TLR4 mut) mice would be more resistant to T/HS-induced gut injury and polymorphonuclear neutrophil (PMN) priming than their wild-type littermates and found that both were significantly reduced in the TLR4 mut mice. In addition, the in vivo and ex vivo PMN priming effect of T/HS intestinal lymph observed in the wild-type mice was abrogated in TLR4 mut mice as well the TRIF mut-deficient mice and partially attenuated in Myd88 mice, suggesting that TRIF activation played a more predominant role than MyD88 in T/HS lymph-induced PMN priming. Polymorphonuclear neutrophil depletion studies showed that T/HS lymph-induced acute lung injury was PMN dependent, because lung injury was totally abrogated in PMN-depleted animals. Because the lymph samples were sterile and devoid of endotoxin or bacterial DNA, we investigated whether the effects of T/HS lymph was related to endogenous nonmicrobial TLR4 ligands. High-mobility group box 1 protein 1, heat shock protein 70, heat shock protein 27, and hyaluronic acid all have been implicated in ischemia-reperfusion-induced tissue injury. None of these "danger" proteins appeared to be involved, because their levels were similar between the sham and shock lymph samples. In conclusion, TLR4 activation is important in T/HS-induced gut injury and in T/HS lymph-induced PMN priming and lung injury. However, the T/HS-associated effects of TLR4 on gut barrier dysfunction can be uncoupled from the T/HS lymph-associated effects of TLR4 on PMN priming.

Efficacy and Tolerability of Fixed-dose Combination of Dexketoprofen and Dicyclomine Injection in Acute Renal Colic Pain Research and Treatment. 2012 | Pubmed ID: 22577544 Objective. To evaluate the efficacy and tolerability of a fixed-dose combination of dexketoprofen and dicyclomine (DXD) injection in patients with acute renal colic. Patients and Methods. Two hundred and seventeen patients were randomized to receive either DXD (n = 109) or fixed-dose combination of diclofenac and dicyclomine injection (DLD; n = 108), intramuscularly. Pain intensity (PI) was self-evaluated by patients on visual analogue scale (VAS) at baseline and at 1, 2, 4, 6, and 8 hours. Efficacy parameters were proportion of responders, difference in PI (PID) at 8 hours, and sum of analogue of pain intensity differences (SAPID). Tolerability was assessed by patients and physicians. Results. DXD showed superior efficacy in terms of proportion of responders (98.17% versus 81.48; P < 0.0001), PID at 8 hours (P = 0.002), and SAPID(0-8â€‰hours) (P = 0.004). The clinical global impression for change in pain was significantly better for DXD than DLD. The incidence of adverse events was comparable in both groups. However, global assessment of tolerability was rated significantly better for DXD. Conclusion. DXD showed superior efficacy and tolerability than DLD in patients clinically diagnosed to be suffering from acute renal colic.

The Effects of Ambient Temperature, Humidity and Season of Year on Urine Composition in Patients with Nephrolithiasis BJU International. Dec, 2012 | Pubmed ID: 22578009 Study Type--Prognosis (cohort series) Level of Evidence 2b. What's known on the subject? and What does the study add? Epidemiologic studies have shown that warmer climates are associated with increased incidence of nephrolithiasis. Many hypothesize that this is due to dehydration and lower urine volumes. The current study of stone formers reports that greater temperatures are associated with significant increases in urine calcium which may shed light on the mechanism underlying the increased stone incidence associated with increased ambient temperature.

Single Cell Profiling of Circulating Tumor Cells: Transcriptional Heterogeneity and Diversity from Breast Cancer Cell Lines PloS One. 2012 | Pubmed ID: 22586443 To improve cancer therapy, it is critical to target metastasizing cells. Circulating tumor cells (CTCs) are rare cells found in the blood of patients with solid tumors and may play a key role in cancer dissemination. Uncovering CTC phenotypes offers a potential avenue to inform treatment. However, CTC transcriptional profiling is limited by leukocyte contamination; an approach to surmount this problem is single cell analysis. Here we demonstrate feasibility of performing high dimensional single CTC profiling, providing early insight into CTC heterogeneity and allowing comparisons to breast cancer cell lines widely used for drug discovery.

Trace Elements Affect Methanogenic Activity and Diversity in Enrichments from Subsurface Coal Bed Produced Water Frontiers in Microbiology. 2012 | Pubmed ID: 22590465 Microbial methane from coal beds accounts for a significant and growing percentage of natural gas worldwide. Our knowledge of physical and geochemical factors regulating methanogenesis is still in its infancy. We hypothesized that in these closed systems, trace elements (as micronutrients) are a limiting factor for methanogenic growth and activity. Trace elements are essential components of enzymes or cofactors of metabolic pathways associated with methanogenesis. This study examined the effects of eight trace elements (iron, nickel, cobalt, molybdenum, zinc, manganese, boron, and copper) on methane production, on mcrA transcript levels, and on methanogenic community structure in enrichment cultures obtained from coal bed methane (CBM) well produced water samples from the Powder River Basin, Wyoming. Methane production was shown to be limited both by a lack of additional trace elements as well as by the addition of an overly concentrated trace element mixture. Addition of trace elements at concentrations optimized for standard media enhanced methane production by 37%. After 7â€‰days of incubation, the levels of mcrA transcripts in enrichment cultures with trace element amendment were much higher than in cultures without amendment. Transcript levels of mcrA correlated positively with elevated rates of methane production in supplemented enrichments (R(2)â€‰=â€‰0.95). Metabolically active methanogens, identified by clone sequences of mcrA mRNA retrieved from enrichment cultures, were closely related to Methanobacterium subterraneum and Methanobacterium formicicum. Enrichment cultures were dominated by M. subterraneum and had slightly higher predicted methanogenic richness, but less diversity than enrichment cultures without amendments. These results suggest that varying concentrations of trace elements in produced water from different subsurface coal wells may cause changing levels of CBM production and alter the composition of the active methanogenic community.

Relationship Between Glomerular Filtration Rate and 24-hour Urine Composition in Patients with Nephrolithiasis Urology. Jul, 2012 | Pubmed ID: 22608801 To examine the relationship between GFR and 24-hour urine composition in patients with nephrolithiasis to understand how renal function may affect stone risk. Alterations in glomerular filtration rate (GFR) are associated with a number of physiological changes.

Effect of Socioeconomic Status on 24-hour Urine Composition in Patients with Nephrolithiasis Urology. Jul, 2012 | Pubmed ID: 22608802 To examine the relationship between the poverty and education levels and 24-hour urine composition in patients with nephrolithiasis because little is known about the relationship between socioeconomic status and kidney stone risk.

The Ontology for Parasite Lifecycle (OPL): Towards a Consistent Vocabulary of Lifecycle Stages in Parasitic Organisms Journal of Biomedical Semantics. 2012 | Pubmed ID: 22621763 Genome sequencing of many eukaryotic pathogens and the volume of data available on public resources have created a clear requirement for a consistent vocabulary to describe the range of developmental forms of parasites. Consistent labeling of experimental data and external data, in databases and the literature, is essential for integration, cross database comparison, and knowledge discovery. The primary objective of this work was to develop a dynamic and controlled vocabulary that can be used for various parasites. The paper describes the Ontology for Parasite Lifecycle (OPL) and discusses its application in parasite research.

Single-neuron Responses in the Human Nucleus Accumbens During a Financial Decision-making Task The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. May, 2012 | Pubmed ID: 22623676 Linking values to actions and evaluating expectations relative to outcomes are both central to reinforcement learning and are thought to underlie financial decision-making. However, neurophysiology studies of these processes in humans remain limited. Here, we recorded the activity of single human nucleus accumbens neurons while subjects performed a gambling task. We show that the nucleus accumbens encodes two signals related to subject behavior. First, we find that under relatively predictable conditions, single neuronal activity predicts future financial decisions on a trial-by-trial basis. Interestingly, we show that this activity continues to predict decisions even under conditions of uncertainty (e.g., when the probability of winning or losing is 50/50 and no particular financial choice predicts a rewarding outcome). Furthermore, we find that this activity occurs, on average, 2 s before the subjects physically manifest their decision. Second, we find that the nucleus accumbens encodes the difference between expected and realized outcomes, consistent with a prediction error signal. We show this activity occurs immediately after the subject has realized the outcome of the trial and is present on both the individual and population neuron levels. These results provide human single neuronal evidence that the nucleus accumbens is integral in making financial decisions.

Inner and Outer Retinal Volumetric and Morphologic Analysis of the Macula with Spectral Domain Optical Coherence Tomography in Retinitis Pigmentosa Middle East African Journal of Ophthalmology. Apr-Jun, 2012 | Pubmed ID: 22623864 To use spectral domain optical coherence tomography (OCT) to assess the features of the inner and outer layers of the macula in subjects with retinitis pigmentosa (RP).

Evaluation of Protective Effect of Butea Monosperma (lam.) Taub in Experimental Hepatotoxicity in Rats Journal of Pharmacology & Pharmacotherapeutics. Apr, 2012 | Pubmed ID: 22629095

Energy Conservation for the Simulation of Deformable Bodies IEEE Transactions on Visualization and Computer Graphics. May, 2012 | Pubmed ID: 22665723 We propose a novel technique that allows one to conserve energy using the time integration scheme of one’s choice. Traditionally, the time integration methods that deal with energy conservation, such as symplectic and variational integrators, have aimed to include damping in a manner independent of the time step size, stating that this gives more control over the look and feel of the simulation. Generally speaking, damping adds to the overall aesthetics of a numerical simulation, especially since it damps out the high frequency oscillations that occur on the level of the discretization mesh. We propose an alternative technique that allows one to use damping to obtain the desired look of a numerical simulation, while still exactly conserving the total energy - in stark contrast to previous methods where adding damping effects necessarily removes energy from the mesh. This allows, for example, a deformable bouncing ball with aesthetically pleasing damping to collide with the ground and return to its original height exactly conserving energy (see Figure 1). Furthermore, since our method works with any time integration scheme, the user can choose their favorite time integration method with regards to aesthetics and simply apply our method as a post-process to conserve all or as much of the energy as desired.

Traditional Systolic Blood Pressure Targets Underestimate Hypotension-induced Secondary Brain Injury The Journal of Trauma and Acute Care Surgery. May, 2012 | Pubmed ID: 22673237 Vital signs, particularly blood pressure, are often manipulated to maximize perfusion and optimize recovery from severe traumatic brain injury (sTBI). We investigated the utility of automated continuously recorded vital signs to predict outcomes after sTBI.

Relationship Between Serum Vitamin D and 24-hour Urine Calcium in Patients with Nephrolithiasis Urology. Nov, 2012 | Pubmed ID: 22698470 To examine the relationship between serum 25-OH vitamin D and 24-hour urine calcium in patients with nephrolithiasis.

Pilot Study of the Correlation of Multiphoton Tomography of Ex Vivo Human Testis with Histology The Journal of Urology. Aug, 2012 | Pubmed ID: 22704107 Although microdissection testicular sperm extraction has become first line therapy for sperm retrieval in men with nonobstructive azoospermia, there are challenges to the procedure, including difficulty differentiating between seminiferous tubules with normal and abnormal spermatogenesis. Multiphoton microscopy illuminates tissue with a near infrared laser to elicit autofluorescence, which enables real-time imaging of unprocessed tissue without labels. We hypothesized that we could accurately characterize seminiferous tubular histology in humans using multiphoton microscopy.

Mechanisms of Deep Brain Stimulation for Obsessive Compulsive Disorder: Effects Upon Cells and Circuits Frontiers in Integrative Neuroscience. 2012 | Pubmed ID: 22712007 Deep brain stimulation (DBS) has emerged as a safe, effective, and reversible treatment for a number of movement disorders. This has prompted investigation of its use for other applications including psychiatric disorders. In recent years, DBS has been introduced for the treatment of obsessive compulsive disorder (OCD), which is characterized by recurrent unwanted thoughts or ideas (obsessions) and repetitive behaviors or mental acts performed in order to relieve these obsessions (compulsions). Abnormal activity in cortico-striato-thalamo-cortical (CSTC) circuits including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), ventral striatum, and mediodorsal (MD) thalamus has been implicated in OCD. To this end a number of DBS targets including the anterior limb of the internal capsule (ALIC), ventral capsule/ventral striatum (VC/VS), ventral caudate nucleus, subthalamic nucleus (STN), and nucleus accumbens (NAc) have been investigated for the treatment of OCD. Despite its efficacy and widespread use in movement disorders, the mechanism of DBS is not fully understood, especially as it relates to psychiatric disorders. While initially thought to create a functional lesion akin to ablative procedures, it is increasingly clear that DBS may induce clinical benefit through activation of axonal fibers spanning the CSTC circuits, alteration of oscillatory activity within this network, and/or release of critical neurotransmitters. In this article we review how the use of DBS for OCD informs our understanding of both the mechanisms of DBS and the circuitry of OCD. We review the literature on DBS for OCD and discuss potential mechanisms of action at the neuronal level as well as the broader circuit level.

Optimizing Read Mapping to Reference Genomes to Determine Composition and Species Prevalence in Microbial Communities PloS One. 2012 | Pubmed ID: 22719831 The Human Microbiome Project (HMP) aims to characterize the microbial communities of 18 body sites from healthy individuals. To accomplish this, the HMP generated two types of shotgun data: reference shotgun sequences isolated from different anatomical sites on the human body and shotgun metagenomic sequences from the microbial communities of each site. The alignment strategy for characterizing these metagenomic communities using available reference sequence is important to the success of HMP data analysis. Six next-generation aligners were used to align a community of known composition against a database comprising reference organisms known to be present in that community. All aligners report nearly complete genome coverage (>97%) for strains with over 6X depth of coverage, however they differ in speed, memory requirement and ease of use issues such as database size limitations and supported mapping strategies. The selected aligner was tested across a range of parameters to maximize sensitivity while maintaining a low false positive rate. We found that constraining alignment length had more impact on sensitivity than does constraining similarity in all cases tested. However, when reference species were replaced with phylogenetic neighbors, similarity begins to play a larger role in detection. We also show that choosing the top hit randomly when multiple, equally strong mappings are available increases overall sensitivity at the expense of taxonomic resolution. The results of this study identified a strategy that was used to map over 3 tera-bases of microbial sequence against a database of more than 5,000 reference genomes in just over a month.

Human Dorsal Anterior Cingulate Cortex Neurons Mediate Ongoing Behavioural Adaptation Nature. Aug, 2012 | Pubmed ID: 22722841 The ability to optimize behavioural performance when confronted with continuously evolving environmental demands is a key element of human cognition. The dorsal anterior cingulate cortex (dACC), which lies on the medial surface of the frontal lobes, is important in regulating cognitive control. Hypotheses about its function include guiding reward-based decision making, monitoring for conflict between competing responses and predicting task difficulty. Precise mechanisms of dACC function remain unknown, however, because of the limited number of human neurophysiological studies. Here we use functional imaging and human single-neuron recordings to show that the firing of individual dACC neurons encodes current and recent cognitive load. We demonstrate that the modulation of current dACC activity by previous activity produces a behavioural adaptation that accelerates reactions to cues of similar difficulty to previous ones, and retards reactions to cues of different difficulty. Furthermore, this conflict adaptation, or Gratton effect, is abolished after surgically targeted ablation of the dACC. Our results demonstrate that the dACC provides a continuously updated prediction of expected cognitive demand to optimize future behavioural responses. In situations with stable cognitive demands, this signal promotes efficiency by hastening responses, but in situations with changing demands it engenders accuracy by delaying responses.

Identification of Novel Mutations in HEXA Gene in Children Affected with Tay Sachs Disease from India PloS One. 2012 | Pubmed ID: 22723944 Tay Sachs disease (TSD) is a neurodegenerative disorder due to Î²-hexosaminidase A deficiency caused by mutations in the HEXA gene. The mutations leading to Tay Sachs disease in India are yet unknown. We aimed to determine mutations leading to TSD in India by complete sequencing of the HEXA gene. The clinical inclusion criteria included neuroregression, seizures, exaggerated startle reflex, macrocephaly, cherry red spot on fundus examination and spasticity. Neuroimaging criteria included thalamic hyperdensities on CT scan/T1W images of MRI of the brain. Biochemical criteria included deficiency of hexosaminidase A (less than 2% of total hexosaminidase activity for infantile patients). Total leukocyte hexosaminidase activity was assayed by 4-methylumbelliferyl-N-acetyl-Î²-D-glucosamine lysis and hexosaminidase A activity was assayed by heat inactivation method and 4-methylumbelliferyl-N-acetyl-Î²-D-glucosamine-6-sulphate lysis method. The exons and exon-intron boundaries of the HEXA gene were bidirectionally sequenced using an automated sequencer. Mutations were confirmed in parents and looked up in public databases. In silico analysis for mutations was carried out using SIFT, Polyphen2, MutationT@ster and Accelrys Discovery Studio softwares. Fifteen families were included in the study. We identified six novel missense mutations, c.340 G>A (p.E114K), c.964 G>A (p.D322N), c.964 G>T (p.D322Y), c.1178C>G (p.R393P) and c.1385A>T (p.E462V), c.1432 G>A (p.G478R) and two previously reported mutations. c.1277_1278insTATC and c.508C>T (p.R170W). The mutation p.E462V was found in six unrelated families from Gujarat indicating a founder effect. A previously known splice site mutation c.805+1 G>C and another intronic mutation c.672+30 T>G of unknown significance were also identified. Mutations could not be identified in one family. We conclude that TSD patients from Gujarat should be screened for the common mutation p.E462V.

Diagnostic Strategy for Mucolipidosis II/III Indian Pediatrics. Dec, 2012 | Pubmed ID: 22728628 Overlapping clinical phenotypes are a diagnostic challenge to the clinician, especially in the cases of mucolipidosis (ML) and mucopolysaccharide disorders (MPS), due to overlapping phenotypes. Present study was carried out in 147 children suspected to have ML or MPS and 100 controls. They were screened for ML II/III by colorimetric method using substrate pNCS. Six children were found screen positive for ML II/III and further confirmatory study showed significantly raised activity in plasma confirming high specificity of the ML screening test. Forty-two (28.5%) children out of remaining 141 children that were screen negative, were found to have various MPS disorders, while rest 99 had normal enzyme activity in plasma and leucocytes. Present study demonstrates prompt and specific chemical method that can be used as a tool for estimating ML II/III, with high specificity.

Intravenous Rt-PA is Not Associated with Increased Risk of Hemorrhage in Patients with Intracranial Aneurysms Neurocritical Care. Jul, 2012 | Pubmed ID: 22752394 The presence of an intracranial aneurysm is listed as an exclusion criterion for the administration of recombinant tissue-plasminogen activator (rt-PA). This study was designed to test the hypothesis that the administration of rt-PA is safe in patients who have an unruptured intracranial aneurysm.

Sleep Shelters Verbal Memory from Different Kinds of Interference Sleep. Jul, 2012 | Pubmed ID: 22754045 Studies have shown that sleep shelters old verbal memories from associative interference arising from new, more recently acquired memories. Our objective is to extend the forms of interference for which sleep provides a sheltering benefit to non-associative and prospective interference, and to examine experimental conditions and memory strengths for which sleep before or after learning particularly affects verbal memory consolidation.

The Greater Cincinnati Pediatric Clinic Repository: A Novel Framework for Childhood Asthma and Allergy Research Pediatric Allergy, Immunology, and Pulmonology. Jun, 2012 | Pubmed ID: 22768387 BACKGROUND: Allergic disorders, including asthma, allergic rhinitis, atopic dermatitis, eosinophilic esophagitis, and food allergy, are a major global health burden. The study and management of allergic disorders is complicated by the considerable heterogeneity in both the presentation and natural history of these disorders. Biorepositories serve as an excellent source of data and biospecimens for delineating subphenotypes of allergic disorders, but such resources are lacking. METHODS: In order to define subphenotypes of allergic disease accurately, we established an infrastructure to link and efficiently utilize clinical and epidemiologic data with biospecimens into a single biorepository called the Greater Cincinnati Pediatric Clinic Repository (GCPCR). Children with allergic disorders as well as healthy controls are followed longitudinally at hospital clinic, emergency department, and inpatient visits. Subjects' asthma, allergy, and skin symptoms; past medical, family, social, diet, and environmental histories; physical activity; medication adherence; perceived quality of life; and demographics are ascertained. DNA is collected from all participants, and other biospecimens such as blood, hair, and nasal epithelial cells are collected on a subset. RESULTS: To date, the GCPCR has 6,317 predominantly Caucasian and African American participants, and 93% have banked DNA. This large sample size supports adequately powered genetic, epidemiologic, environmental, and health disparities studies of childhood allergic diseases. CONCLUSIONS: The GCPCR is a unique biorepository that is continuously evaluated and refined to achieve and maintain rigorous clinical phenotype and biological data. Development of similar disease-specific repositories using common data elements is necessary to enable studies across multiple populations of comprehensively phenotyped patients.

Early Signs of Longitudinal Progressive Cone Photoreceptor Degeneration in Achromatopsia The British Journal of Ophthalmology. Sep, 2012 | Pubmed ID: 22790432 To characterise longitudinal progressive retinal changes in achromatopsia.

Efficacy of Narrowband Ultraviolet B Versus Excimer Radiation in Repigmenting Vitiligo After Minigrafting on the Distal Arms Journal of the American Academy of Dermatology. Aug, 2012 | Pubmed ID: 22794808

Small Ischemic Lesions Following Intracerebral Hemorrhage: Silent but Deadly Neurology. Aug, 2012 | Pubmed ID: 22843276

In Utero Fetal Ovarian Torsion with Imaging Findings on Ultrasound and MRI Case Reports in Radiology. 2012 | Pubmed ID: 22844628 Early diagnosis of ovarian torsion is critical in avoiding complications and planning management. Therefore, it is important to understand and assess the imaging findings of ovarian torsion. Ultrasound is the imaging modality of choice; however, it is not always definitive and diagnosis can be challenging. MRI is a better imaging modality to evaluate for signs of complications and to arrive at a more definitive diagnosis. We present a case of in utero ovarian torsion diagnosed during routine prenatal ultrasound with imaging findings on ultrasound and MRI postnatally.

The Coronary CT Angiography Vision Protocol: a Prospective Observational Imaging Cohort Study in Patients Undergoing Non-cardiac Surgery BMJ Open. 2012 | Pubmed ID: 22855630 At present, physicians have a limited ability to predict major cardiovascular complications after non-cardiac surgery and little is known about the anatomy of coronary arteries associated with perioperative myocardial infarction. We have initiated the Coronary CT Angiography (CTA) VISION Study to (1) establish the predictive value of coronary CTA for perioperative myocardial infarction and death and (2) describe the coronary anatomy of patients that have a perioperative myocardial infarction.

Neuroprotective Activityof Cymbopogon Martinii Against Cerebral Ischemia/reperfusion-induced Oxidative Stress in Rats Journal of Ethnopharmacology. Jun, 2012 | Pubmed ID: 22855942 Cymbopogon martinii (Roxb.) Watson (Family: Graminae), commonly known as Palmarosa, is traditionally prescribed for central nervous system (CNS) disorders such as neuralgia, epileptic fits and anorexia. Although the plant possesses diverse pharmacological actions, the neuroprotective action has got little attention.

Dermoid Cyst: A Rare Intramedullary Inclusion Cyst Asian Journal of Neurosurgery. Apr, 2012 | Pubmed ID: 22870157 Intramedullary dermoid cysts are rare tumors, especially those not associated with spinal dysraphism. Only six cases have been reported in the literature. Of these, only two cases have had magnetic resonance imaging studies. We report a case of an 18-year-old female patient, who presented with progressive weakness of both the lower limbs and wasting of both the upper limbs. Magnetic resonance imaging (MRI) showed an intramedullary lesion extending from C3 to D2 with peripheral enhancement on contrast. Decompression of the cystic contents with partial removal of cyst wall was done. Hair with oily cholesterol and keratin debris was encountered. Histopathology confirmed the diagnosis of dermoid cyst. This case adds to the previous reported cases of the rare and uncommon intramedullary space occupying lesions of the spinal cord.

Identifying Risk Factors in Renal Allografts Before Transplant: Machine-measured Renal Resistance and Posttransplant Allograft Survival Progress in Transplantation (Aliso Viejo, Calif.). Jun, 2012 | Pubmed ID: 22878075 Enhancement of renal allograft function and survival in an era where expanded criteria donors are increasingly used requires validated selection criteria. The goal of this retrospective study was to evaluate the significance of pretransplant donor and allograft parameters to identify risk factors that can be used in a model to predict 1-year allograft outcomes. Donor demographic factors, donor type, and allograft parameters such as biopsy results and machine-measured renal resistance were correlated with 1-year graft outcome. The Kaplan-Meier method was used to estimate graft survival using the categorical predictors of donor type, donor age, and machine measured renal resistance at 1.5, 3, and 5 hours. The log-rank test was used to test the difference in survival curves between cohorts. The Cox regression analysis was used to estimate hazard ratios for machine-measured renal resistance, donor age, donor terminal creatinine level, donor's estimated glomerular filtration rate, cold ischemia time, and percent glomerulosclerosis. The data show that machine-measured renal resistance at 3 and 5 hours has a statistically significant inverse relationship to 1-year graft survival. All other risk factors had no correlation with 1-year graft survival. The machine-measured renal resistance at 3 hours is the earliest significant predictor of 1-year allograft outcome.

Discovering Fine-grained Sentiment in Suicide Notes Biomedical Informatics Insights. 2012 | Pubmed ID: 22879770 This paper presents our solution for the i2b2 sentiment classification challenge. Our hybrid system consists of machine learning and rule-based classifiers. For the machine learning classifier, we investigate a variety of lexical, syntactic and knowledge-based features, and show how much these features contribute to the performance of the classifier through experiments. For the rule-based classifier, we propose an algorithm to automatically extract effective syntactic and lexical patterns from training examples. The experimental results show that the rule-based classifier outperforms the baseline machine learning classifier using unigram features. By combining the machine learning classifier and the rule-based classifier, the hybrid system gains a better trade-off between precision and recall, and yields the highest micro-averaged F-measure (0.5038), which is better than the mean (0.4875) and median (0.5027) micro-average F-measures among all participating teams.

Role of Lipase-generated Free Fatty Acids in Converting Mesenteric Lymph from a Noncytotoxic to a Cytotoxic Fluid American Journal of Physiology. Gastrointestinal and Liver Physiology. Oct, 2012 | Pubmed ID: 22899820 Recent studies have shown that mesenteric lymph plays a very important role in the development of multiple-organ dysfunction syndrome under critical conditions. Great efforts have been made to identify the biologically active molecules in the lymph. We used a trauma-hemorrhagic shock (T/HS) model and the superior mesenteric artery occlusion (SMAO) model, representing a global and a localized intestinal ischemia-reperfusion insult, respectively, to investigate the role of free fatty acids (FFAs) in the cytotoxicity of mesenteric lymph in rats. Lymph was collected before, during, and after (post) shock or SMAO. The post-T/HS and SMAO lymph, but not the sham lymph, manifested cytotoxicity for human umbilical vein endothelial cells (HUVECs). HUVEC cytotoxicity was associated with increased FFAs, especially the FFA-to-protein ratio. Addition of albumin, especially delipidated albumin, reduced this cytotoxicity. Lipase treatment of trauma-sham shock (T/SS) lymph converted it from a noncytotoxic to a cytotoxic fluid, and its toxicity correlated with the FFA-to-protein ratio in a fashion similar to that of the T/HS lymph, further suggesting that FFAs were the key components leading to HUVEC cytotoxicity. Analysis of lymph by gas chromatography revealed that the main FFAs in the post-T/HS or lipase-treated T/SS lymph were palmitic, stearic, oleic, and linoleic acids. When added to the cell culture at levels comparable to those in T/HS lymph, all these FFAs were cytotoxic, with linoleic acid being the most potent. In conclusion, this study suggests that lipase-generated FFAs are the key components resulting in the cytotoxicity of T/HS and SMAO mesenteric lymph.

ACR Appropriateness CriteriaÂ® Acute Onset Flank Pain--suspicion of Stone Disease Ultrasound Quarterly. Sep, 2012 | Pubmed ID: 22902840 Low dose (

The Use of Synthetic Mesh and the Management of Mesh Extrusion in Vaginal Surgery Expert Review of Medical Devices. Jul, 2012 | Pubmed ID: 22905847 The authors present a review of the literature regarding the management of mesh extrusion in vaginal surgery. As used in traditional surgical techniques, the use of mesh theoretically allows for a broader base of support and eliminates the need to rely on pre-existing weakened fascia. In this article, the different physical properties and types of synthetic mesh used, and their respective advantages and disadvantages in terms of mesh extrusion, are reviewed.

Gene Expression Correlates with Process Rates Quantified for Sulfate- and Fe(III)-Reducing Bacteria in U(VI)-Contaminated Sediments Frontiers in Microbiology. 2012 | Pubmed ID: 22908009 Though iron- and sulfate-reducing bacteria are well known for mediating uranium(VI) reduction in contaminated subsurface environments, quantifying the in situ activity of the microbial groups responsible remains a challenge. The objective of this study was to demonstrate the use of quantitative molecular tools that target mRNA transcripts of key genes related to Fe(III) and sulfate reduction pathways in order to monitor these processes during in situ U(VI) remediation in the subsurface. Expression of the Geobacteraceae-specific citrate synthase gene (gltA) and the dissimilatory (bi)sulfite reductase gene (dsrA), were correlated with the activity of iron- or sulfate-reducing microorganisms, respectively, under stimulated bioremediation conditions in microcosms of sediments sampled from the U.S. Department of Energy's Oak Ridge Integrated Field Research Challenge (OR-IFRC) site at Oak Ridge, TN, USA. In addition, Geobacteraceae-specific gltA and dsrA transcript levels were determined in parallel with the predominant electron acceptors present in moderately and highly contaminated subsurface sediments from the OR-IFRC. Phylogenetic analysis of the cDNA generated from dsrA mRNA, sulfate-reducing bacteria-specific 16S rRNA, and gltA mRNA identified activity of specific microbial groups. Active sulfate reducers were members of the Desulfovibrio, Desulfobacterium, and Desulfotomaculum genera. Members of the subsurface Geobacter clade, closely related to uranium-reducing Geobacter uraniireducens and Geobacter daltonii, were the metabolically active iron-reducers in biostimulated microcosms and in situ core samples. Direct correlation of transcripts and process rates demonstrated evidence of competition between the functional guilds in subsurface sediments. We further showed that active populations of Fe(III)-reducing bacteria and sulfate-reducing bacteria are present in OR-IFRC sediments and are good potential targets for in situ bioremediation.

High Dietary Magnesium Intake Decreases Hyperoxaluria in Patients with Nephrolithiasis Urology. Oct, 2012 | Pubmed ID: 22921695 To examine the relationship between urine magnesium and hyperoxaluria in a cohort of patients with recurrent stone formation.

Abnormalities of 24-hour Urine Composition in First-time and Recurrent Stone-formers Urology. Oct, 2012 | Pubmed ID: 22921696 To examine differences in 24-hour urine composition between recurrent and first-time stone-formers.

Intravitreal Ranibizumab Versus Bevacizumab for Treatment of Myopic Choroidal Neovascularization Retina (Philadelphia, Pa.). Sep, 2012 | Pubmed ID: 22922846 To compare intravitreal bevacizumab (IVB) and intravitreal ranibizumab (IVR) in the treatment of subfoveal choroidal neovascularization associated with pathologic myopia.

The Storage Lesion of Packed Red Blood Cells Affects Coagulation Surgery. Oct, 2012 | Pubmed ID: 22939747 The storage lesion of packed red blood cells (PRBCs) consists of biochemical changes associated with increased inflammatory mediators and decreased oxygen-carrying capacity. The effect of storage on the coagulation system is less well studied. The purpose of this study is to determine how PRBC storage time affects the activated coagulation time (ACT), using an inÂ vitro model.

Role of Delayed Light Polymerization of a Dual-cured Composite Base on Marginal Adaptation of Class II Posterior Composite Open-sandwich Restoration Indian Journal of Dental Research : Official Publication of Indian Society for Dental Research. Mar-Apr, 2012 | Pubmed ID: 22945734 To determine the effect of delayed light polymerization of a dual-cured composite base material on the marginal adaptation of class II composite restoration.

Conflict of Interest in Spine Research Reporting PloS One. 2012 | Pubmed ID: 22952956 Medical studies are more likely to report favorable findings when a conflict of interest is declared. We aim to quantify and determine the effect of author disclosure of conflict of interest on scientific reporting.

In Vivo Optical Molecular Imaging of Matrix Metalloproteinase Activity Following Celecoxib Therapy for Colorectal Cancer Molecular Imaging. Sep-Oct, 2012 | Pubmed ID: 22954186 We present an optical molecular imaging approach to measure the efficacy of the cyclooxygenase-2 (COX-2) inhibitor celecoxib on tumor growth rate through its effect on matrix metalloproteinase (MMP) activity. A xenograft model of colorectal cancer was generated in nude mice, which were then randomized to receive celecoxib versus vehicle. MMP activity was measured by an enzyme-activatable optical molecular probe. A novel genetically engineered mouse (GEM) model of colorectal cancer was also used to assess celecoxib's effect on MMP activity, which was measured by quantitative fluorescence colonoscopy. Subcutaneously implanted xenograft tumors were 84% (SD 20.2%) smaller in volume in the treatment group versus the control group. Moreover, treated animals exhibited only a 7.6% (SEM 9%) increase in MMP activity versus 106% (SEM 8%) for untreated animals. There was an apparent linear relationship (r â€Š=â€Š .91) between measured MMP activity and tumor growth rate. Finally, in the GEM model experiment, treated murine tumors remained relatively unchanged in volume and MMP activity; however, untreated tumors grew significantly and showed an increase in MMP activity. This method may provide for the improved identification of patients for whom COX-2 inhibition therapy is indicated by allowing one to balance the patient's cardiovascular risk with the cancer's responsiveness to celecoxib.

Confounding by Indication in Retrospective Studies of Intracerebral Hemorrhage: Antiepileptic Treatment and Mortality Neurocritical Care. Dec, 2012 | Pubmed ID: 22965324 Intracerebral hemorrhage (ICH) is a highly fatal disease with few proven treatments. Data to guide clinician decisions for therapies, including antiepileptic drugs (AED), are limited. Published studies on AED treatment in ICH have provided conflicting results. We investigated the effect of AED treatment on 90-day mortality after ICH in a large prospectively ascertained cohort.

Does Inhibiting Sur1 Complement Rt-PA in Cerebral Ischemia? Annals of the New York Academy of Sciences. Sep, 2012 | Pubmed ID: 22994227 Hemorrhagic transformation (HT) associated with recombinant tissue plasminogen activator (rt-PA) complicates and limits its use in stroke. Here, we provide a focused review on the involvement of matrix metalloproteinase 9 (MMP-9) in rt-PA-associated HT in cerebral ischemia, and we review emerging evidence that the selective inhibitor of the sulfonylurea receptor 1 (Sur1), glibenclamide (U.S. adopted name, glyburide), may provide protection against rt-PA-associated HT in cerebral ischemia. Glyburide inhibits activation of MMP-9, ameliorates edema formation, swelling, and symptomatic hemorrhagic transformation, and improves preclinical outcomes in several clinically relevant models of stroke, both without and with rt-PA treatment. A retrospective clinical study comparing outcomes in diabetic patients with stroke treated with rt-PA showed that those who were previously on and were maintained on a sulfonylurea fared significantly better than those whose diabetes was managed without sulfonylureas. Inhibition of Sur1 with injectable glyburide holds promise for ameliorating rt-PA-associated HT in stroke.

Neurocritical Care and Periprocedural Blood Pressure Management in Acute Stroke Neurology. Sep, 2012 | Pubmed ID: 23008398 The purpose of this article is to review the literature on periprocedural blood pressure (BP) management in acute ischemic stroke and to establish guidelines regarding management of BP. These guidelines are drawn from available evidence and expert opinion. This article reviews the pathophysiologic considerations of BP in ischemic stroke. It also examines the natural history of BP changes during stroke, as well as data on induced BP reduction and hypertension, particularly in light of reperfusion therapy. Finally, the article reviews major ongoing clinical trials for BP management in this setting. Recommendations made in this article may serve as a benchmark for future research in BP management in this patient population.

Predictive Value of Bronchoscopy After Infant Cardiac Surgery: a Prospective Study Intensive Care Medicine. Nov, 2012 | Pubmed ID: 23011533 Airway evaluation following infant cardiac surgery often reveals evidence of tracheobronchial narrowing. We studied the association between airway narrowing and extubation failure (EF) in this population.

Low-sodium Dietary Approaches to Stop Hypertension Diet Reduces Blood Pressure, Arterial Stiffness, and Oxidative Stress in Hypertensive Heart Failure with Preserved Ejection Fraction Hypertension. Nov, 2012 | Pubmed ID: 23033371 Recent studies suggest that oxidative stress and vascular dysfunction contribute to heart failure with preserved ejection fraction (HFPEF). In salt-sensitive HFPEF animal models, diets low in sodium and high in potassium, calcium, magnesium, and antioxidants attenuate oxidative stress and cardiovascular damage. We hypothesized that the sodium-restricted Dietary Approaches to Stop Hypertension diet (DASH/SRD) would have similar effects in human hypertensive HFPEF. Thirteen patients with treated hypertension and compensated HFPEF consumed the DASH/SRD for 21 days (all food/most beverages provided). The DASH/SRD reduced clinic systolic (155-138 mmâ€‰Hg; P=0.02) and diastolic blood pressure (79-72 mmâ€‰Hg; P=0.04), 24-hour ambulatory systolic (130-123 mmâ€‰Hg; P=0.02) and diastolic blood pressure (67-62 mmâ€‰Hg; P=0.02), and carotid-femoral pulse wave velocity (12.4-11.0 m/s; P=0.03). Urinary F2-isoprostanes decreased by 31% (209-144 pmol/mmol Cr; P=0.02) despite increased urinary aldosterone excretion. The reduction in urinary F2-isoprostanes closely correlated with the reduction in urinary sodium excretion on the DASH/SRD. In this cohort of HFPEF patients with treated hypertension, the DASH/SRD reduced systemic blood pressure, arterial stiffness, and oxidative stress. These findings are characteristic of salt-sensitive hypertension, a phenotype present in many HFPEF animal models and suggest shared pathophysiological mechanisms linking these 2 conditions. Further dietary modification studies could provide insights into the development and progression of hypertensive HFPEF.

Population Genetic Inference from Personal Genome Data: Impact of Ancestry and Admixture on Human Genomic Variation American Journal of Human Genetics. Oct, 2012 | Pubmed ID: 23040495 Full sequencing of individual human genomes has greatly expanded our understanding of human genetic variation and population history. Here, we present a systematic analysis of 50 human genomes from 11 diverse global populations sequenced at high coverage. Our sample includes 12 individuals who have admixed ancestry and who have varying degrees of recent (within the last 500 years) African, Native American, and European ancestry. We found over 21 million single-nucleotide variants that contribute to a 1.75-fold range in nucleotide heterozygosity across diverse human genomes. This heterozygosity ranged from a high of one heterozygous site per kilobase in west African genomes to a low of 0.57 heterozygous sites per kilobase in segments inferred to have diploid Native American ancestry from the genomes of Mexican and Puerto Rican individuals. We show evidence of all three continental ancestries in the genomes of Mexican, Puerto Rican, and African American populations, and the genome-wide statistics are highly consistent across individuals from a population once ancestry proportions have been accounted for. Using a generalized linear model, we identified subtle variations across populations in the proportion of neutral versus deleterious variation and found that genome-wide statistics vary in admixed populations even once ancestry proportions have been factored in. We further infer that multiple periods of gene flow shaped the diversity of admixed populations in the Americas-70% of the European ancestry in today's African Americans dates back to European gene flow happening only 7-8 generations ago.

Neurosurgical Treatment of Cushing Disease Neurosurgery Clinics of North America. Oct, 2012 | Pubmed ID: 23040749 Cushing disease (CD) is caused by overproduction of adrenocorticotropin by a pituitary adenoma (or, rarely, carcinoma). The diagnosis of CD requires distinguishing it from other hypercortisolemic states with a thorough endocrine workup. CD remains a primarily surgical disease, with remission rates of 70% to 95% following microscopic or endoscopic transsphenoidal surgery.

Enhancing Risk Prediction with PET Coronary Flow Reserve: Can It Be Clinically Useful? JACC. Cardiovascular Imaging. Oct, 2012 | Pubmed ID: 23058071

Evidence That Temporal Lobe is a Default Area in Absence Epilepsy Epilepsy & Behavior : E&B. Oct, 2012 | Pubmed ID: 23059065 Correctly classifying seizures is essential for appropriate epilepsy management. Focal and generalized epilepsy rarely occur independently in the same patient. Cases of focal ictal evolution during seizures that are generalized in onset have been reported though these have included a small heterogeneous series of patients with generalized epilepsy and features on the EEG. We wish to report two patients with absence epilepsy that were noted on video-EEG monitoring to manifest a focal temporal electroclinical transformation from a typical absence seizure. Defining the electroclinical spectrum of absence seizures could add to our understanding of the selective cortical and subcortical networks that are involved in patients with "prototypic" generalized and focal seizures.

Unique Case of a Geminated Supernumerary Tooth with Trifid Crown Imaging Science in Dentistry. Sep, 2012 | Pubmed ID: 23071971 Gemination, a relatively uncommon dental anomaly, is characterized by its peculiar representation as a tooth with a bifid crown and a common root and root canal. It usually occurs in primary dentition. To come across gemination in a supernumerary tooth is a rare phenomenon. The purpose of this paper is to present a unique case of hyperdontia wherein gemination in an impacted supernumerary tooth resulted in a trifid crown unlike the usual bifid crown. The role of conventional radiographs as well as computed tomography, to accurately determine the morphology and spatial location, and to arrive at a diagnosis, is also emphasized in this paper.

Role of MDCT Angiography in Selection and Presurgical Planning of Potential Renal Donors AJR. American Journal of Roentgenology. Nov, 2012 | Pubmed ID: 23096176 The purpose of this study was to determine the prevalence and types of renal and extrarenal abnormalities that preclude renal donation or lead to alteration of the surgical approach on the basis of abdominal CT angiography (CTA) in a large group of potential renal donors.

Efficacy and Tolerability of Pharmacotherapy Options for the Treatment of Medullary Thyroid Cancer Clinical Medicine Insights. Oncology. 2012 | Pubmed ID: 23133319 Metastatic and unresectable medullary thyroid carcinoma (MTC) is often difficult to treat as it is relatively unresponsive to radiation and conventional chemotherapy. This emphasizes the importance of the development of targeted therapies for advanced MTC. Vandetanib was approved by the US Food and Drug Administration for the treatment of symptomatic or progressive MTC in patients with advanced disease in April 2011. This therapy proved to be a breakthrough in the management of MTC. We review the efficacy and safety of this novel treatment and other treatments that are being evaluated in this disease.

Screening for Injurious Falls in Acute Care Hospitals Journal of Patient Safety. Nov, 2012 | Pubmed ID: 23149691 BACKGROUND: Injurious fall is a serious hospital-acquired condition. Screening tools for injurious falls in hospitalized patients have received limited evaluation. OBJECTIVE: To compare operating characteristics of a succinct screening tool for injurious falls, the University of Pittsburgh Medical Center (UPMC) screening tool (based on mobility, fall history, and nursing judgment), with the ABCS injurious fall screening tool (based on Age, Bone, Coagulation, and recent Surgery). DESIGN: Case control study. METHODS: Hospitalized patients with injurious falls were identified from the UPMC adverse events database for 2007-2008 (N = 43). Controls (n = 86) matched for age, location, and period of fall event were selected from the hospital's administrative database. Tools were evaluated independently by 2 screeners using electronic charts. Interrater agreement, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and c-statistics for the screening tools were calculated. RESULTS: Case and control groups were similar in age, sex, and race. Interrater agreement was 71% for ABCS and 72% for UPMC screens. ABCS and UPMC screens had sensitivity of 60.5% (95% CI, 52.0%-68.9%) and 62.8% (95% CI, 54.5%-71.1%), specificity of 41.9% (95% CI, 33.4%-50.4%) and 58.1% (95% CI 49.6%-66.7%), and c-statistics of 51.2% and 59.3%, respectively. With a 33% prevalence of injurious fall, the PPV was 34.2%, and NPV was 67.9% for ABCS, and the PPV was 42.9%, and NPV was 75.8% for UPMC. Operating characteristics were not statistically significantly different, although the UPMC screen was 8% more accurate in predicting injurious falls and had a lower false-positive rate (44.2% versus 65.1%). CONCLUSIONS: Compared with the ABCS screen, the UPMC screen is a simple, practical tool. Prospective studies are needed to establish the UPMC tool's predictive value in hospital practices with lower rates of injurious falls. In general, better screening tools for injurious falls should be developed to meet quality standards.

Dysregulation of IRP1-mediated Iron Metabolism Causes Gamma Ray-specific Radioresistance in Leukemia Cells PloS One. 2012 | Pubmed ID: 23155415 Iron is required for nearly all organisms, playing important roles in oxygen transport and many enzymatic reactions. Excess iron, however, can be cytotoxic. Emerging evidence suggests that radioresistance can be achieved in lower organisms by the protection of proteins, but not DNA, immediately following ionizing radiation (IR) exposure, allowing for improved DNA repair. One potential mechanism for protein protection is controlling and limiting the amount of free iron in cells, as has been demonstrated in the extremophile Deinococcus Radiodurans, reducing the potential for oxidative damage to proteins during exposure to IR. We found that iron regulatory protein 1 (IRP1) expression was markedly reduced in human myeloid leukemia HL60 cells resistant to low linear energy transfer (LET) gamma rays, but not to high LET alpha particles. Stable knockdown of IRP1 by short-hairpin RNA (shRNA) interference in radiosensitive parental cells led to radioresistance to low LET IR, reduced intracellular Fenton chemistry, reduced protein oxidation, and more rapid DNA double-strand break (DSB) repair. The mechanism of radioresistance appeared to be related to attenuated free radical-mediated cell death. Control of intracellular iron by IRPs may be a novel radioresistance mechanism in mammalian cells.

Lesion Procedures in Psychiatric Neurosurgery World Neurosurgery. Nov, 2012 | Pubmed ID: 23159652 Lesion procedures for psychiatric indications have a history that spans more than a century. This review provides a brief history of psychiatric surgery and addresses the most recent literature on lesion surgery for the treatment of anxiety and mood disorders.

Encoding of Rules by Neurons in the Human Dorsolateral Prefrontal Cortex Cerebral Cortex (New York, N.Y. : 1991). Nov, 2012 | Pubmed ID: 23172774 We use rules to extend learned behavior beyond specific instances to general scenarios. The prefrontal cortex (PFC) is thought to play an important role in representing rules, as evidenced by subjects who have difficulty in following rules after PFC damage and by animal studies demonstrating rule sensitivity of individual PFC neurons. How rules are instantiated at the single-neuronal level in the human brain, however, remains unclear. Here, we recorded from individual neurons in the human dorsolateral prefrontal cortex (DLPFC) as subjects performed a task in which they evaluated pairs of images using either of 2 abstract rules. We find that DLPFC neurons selectively encoded these rules while carrying little information about the subjects' responses or the sensory cues used to guide their decisions.

Aortic Vascular Inflammation in Psoriasis is Associated with HDL Particle Size and Concentration: a Pilot Study American Journal of Cardiovascular Disease. 2012 | Pubmed ID: 23173102 Psoriasis is a model Th1-mediated inflammatory disease associated with increased incidence of stroke and cardiovascular disease (CVD). The mechanism behind these associations is unknown, however abnormal HDL particle composition measured by nuclear magnetic resonance (NMR) spectroscopy has been shown to be associated with CVD. Using [18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT), a validated surrogate marker of CVD, we assessed whether HDL particle size and concentration were associated with vascular inflammation in patients with psoriasis. Patients with psoriasis were prospectively enrolled (439 aortic samples from 10 patients). Lipoprotein profiles using NMR spectroscopy were obtained and the relationship between vascular inflammation within the thoracic aorta by FDG-PET/CT was analyzed for association with lipoprotein particle characteristics. The plasma total cholesterol (206 mg/dL (IQR 154-229)), LDL (105 (90-161)), and triglyceride levels were within normal range (151 (94-191)) while HDL levels were low (28.9 (27.2-31.3)); however, the NMR profile demonstrated an atherogenic profile with increased small LDL and HDL particles. Total HDL particle concentration (p

Identification of Novel Mutations in FAH Gene and Prenatal Diagnosis of Tyrosinemia in Indian Family Case Reports in Genetics. 2012 | Pubmed ID: 23193487 Carrier of tyrosinemia type I was diagnosed by sequencing FAH (fumarylacetoacetate hydrolase) gene. It leads to the identification of heterozygous status for both c.648C>G (p.Ile216Met) and c.1159G>A (p.Gly387Arg) mutations in exons 8 and 13, respectively, in the parents. The experimental program PolyPhen, SIFT, and MT predicts former missense point mutation as "benign" that creates a potential donor splice site and later one as "probably damaging" which disrupts secondary structure of protein.

Genotype-Phenotype Characterization of Wolf-Hirschhorn Syndrome Confirmed by FISH: Case Reports Case Reports in Genetics. 2012 | Pubmed ID: 23227376 The Wolf-Hirschhorn syndrome (WHS) is a multiple malformation and contiguous gene syndrome resulting from the deletion encompassing a 4p16.3 region. A microscopically visible terminal deletion on chromosome 4p (4p16â†’pter) was detected in Case 1 with full blown features of WHS. The second case which had an interstitial microdeletion encompassing WHSC 1 and WHSC 2 genes at 4p16.3 presented with less striking clinical features of WHS and had an apparently "normal" karyotype. The severity of the clinical presentation was as a result of haploinsufficiency and interaction with surrounding genes as well as mutations in modifier genes located outside the WHSCR regions. The study emphasized that an individual with a strong clinical suspicion of chromosomal abnormality and a normal conventional cytogenetic study should be further investigated using molecular cytogenetic techniques such as fluorescence in situ hybridization (FISH) or array-comparative genomic hybridization (a-CGH).

Hox Genes Regulate Digit Patterning by Controlling the Wavelength of a Turing-type Mechanism Science (New York, N.Y.). Dec, 2012 | Pubmed ID: 23239739 The formation of repetitive structures (such as stripes) in nature is often consistent with a reaction-diffusion mechanism, or Turing model, of self-organizing systems. We used mouse genetics to analyze how digit patterning (an iterative digit/nondigit pattern) is generated. We showed that the progressive reduction in Hoxa13 and Hoxd11-Hoxd13 genes (hereafter referred to as distal Hox genes) from the Gli3-null background results in progressively more severe polydactyly, displaying thinner and densely packed digits. Combined with computer modeling, our results argue for a Turing-type mechanism underlying digit patterning, in which the dose of distal Hox genes modulates the digit period or wavelength. The phenotypic similarity with fish-fin endoskeleton patterns suggests that the pentadactyl state has been achieved through modification of an ancestral Turing-type mechanism.

Acral Cutaneous Neural Angiomatous Hamartoma: a Variant of Palmar Cutaneous Hamartoma? Case Reports in Dermatological Medicine. 2012 | Pubmed ID: 23259093 Hamartomas are benign malformations composed of tissue elements normally found at that site, but which are growing in a disorganized fashion. Cutaneous hamartomas containing only neural and/or neurovascular elements are very rare, with very few case reports in the literature. Herein we describe a case of congenital neural angiomatous hamartoma of the skin.

Resveratrol Reduces Prostate Cancer Growth and Metastasis by Inhibiting the Akt/MicroRNA-21 Pathway PloS One. 2012 | Pubmed ID: 23272133 The consumption of foods containing resveratrol produces significant health benefits. Resveratrol inhibits cancer by reducing cell proliferation and metastasis and by inducing apoptosis. These actions could be explained by its ability to inhibit (ERK-1/2), Akt and suppressing the levels of estrogen and insulin growth factor -1 (IGF-1) receptor. How these processes are manifested into the antitumor actions of resveratrol is not clear. Using microarray studies, we show that resveratrol reduced the expression of various prostate-tumor associated microRNAs (miRs) including miR-21 in androgen-receptor negative and highly aggressive human prostate cancer cells, PC-3M-MM2. This effect of resveratrol was associated with reduced cell viability, migration and invasiveness. Additionally, resveratrol increased the expression of tumor suppressors, PDCD4 and maspin, which are negatively regulated by miR-21. Short interfering (si) RNA against PDCD4 attenuated resveratrol's effect on prostate cancer cells, and similar effects were observed following over expression of miR-21 with pre-miR-21 oligonucleotides. PC-3M-MM2 cells also exhibited high levels of phospho-Akt (pAkt), which were reduced by both resveratrol and LY294002 (a PI3-kinase inhibitor). MiR-21 expression in these cells appeared to be dependent on Akt, as LY294002 reduced the levels of miR-21 along with a concurrent increase in PDCD4 expression. These in vitro findings were further corroborated in a severe combined immunodeficient (SCID) mouse xenograft model of prostate cancer. Oral administration of resveratrol not only inhibited the tumor growth but also decreased the incidence and number of metastatic lung lesions. These tumor- and metastatic-suppressive effects of resveratrol were associated with reduced miR-21 and pAkt, and elevated PDCD4 levels. Similar anti-tumor effects of resveratrol were observed in DU145 and LNCaP prostate cancer cells which were associated with suppression of Akt and PDCD4, but independent of miR-21.These data suggest that resveratrol's anti-tumor actions in prostate cancer could be explained, in part, through inhibition of Akt/miR-21 signaling pathway.

Species-level Classification of the Vaginal Microbiome BMC Genomics. 2012 | Pubmed ID: 23282177 The application of next-generation sequencing to the study of the vaginal microbiome is revealing the spectrum of microbial communities that inhabit the human vagina. High-resolution identification of bacterial taxa, minimally to the species level, is necessary to fully understand the association of the vaginal microbiome with bacterial vaginosis, sexually transmitted infections, pregnancy complications, menopause, and other physiological and infectious conditions. However, most current taxonomic assignment strategies based on metagenomic 16S rDNA sequence analysis provide at best a genus-level resolution. While surveys of 16S rRNA gene sequences are common in microbiome studies, few well-curated, body-site-specific reference databases of 16S rRNA gene sequences are available, and no such resource is available for vaginal microbiome studies.

Examination of Survival After Transfer from Peritoneal Dialysis to Hemodialysis Advances in Peritoneal Dialysis. Conference on Peritoneal Dialysis. 2012 | Pubmed ID: 23311216 Data on survival after transfer from peritoneal dialysis (PD) to hemodialysis (HD) is conflicting. We reviewed two decades of outcomes in a PD program to examine short-term survival after transfer from PD to HD. Of 379 patients on PD, 33% transferred to HD. The reasons for transfer were PD-related infections (340%), uremia or failure to thrive (26%), PD catheter problems or loss of mechanical skills (15%), dementia or unable to train (7%), noncompliant with PD (7%), other (10%, including gastrointestinal complications, hernia, encapsulating peritoneal sclerosis, preference, loss of ultrafiltration), and cardiac (2%). All of those transferring for "other" reasons survived 6 months, and as did all except 1 who transferred for uremia (p = 0.035). Overall survival was 92% at 3 months and 85% at 6 months. Using multivariate logistic regression analysis, only score on the Charlson comorbidity index at PD start was a risk factor for dying in the first 6 months on HD: for each 1 point increase in CCI score, the hazard ratio for death was 1.4 (95% confidence interval: 1.16 to 1.74; p = 0.005). To summarize, starting a patient on PD and waiting until uremia to transfer to HD does not have a negative impact on survival. In a program with relatively low PD-related infectious complications, such complications accounted for only one third of transfers to HD.

Gain of Chromosome 4qter and Loss of 5pter: an Unusual Case with Features of Cri Du Chat Syndrome Case Reports in Genetics. 2012 | Pubmed ID: 23320207 Here, we present a case with an unusual chromosomal rearrangement in a child with a predominant phenotype of high-pitched crying showing deletion encompassing CTNND2 due to an unbalanced translocation of chromosomes 4 and 5. This rearrangement led to a duplication ofâ€‰~35â€‰Mb in 4qter which replaced 18â€‰Mb genetic materials in 5pter. Even though, in this patient, there was no clinically obvious modification to the classical phenotypes of CdCS, and the influence of the 4q-duplication cannot be completely excluded in this case. However, the region 4q34.1-34.3 was previously reported as a region not leading to phenotypic changes if present in three copies, an observation which could possibly be supported by this case. Conclusion. This study showed that in a patient with an unbalanced translocation resulting in 5p deletion, the presence of partial trisomy of chromosome 4q could be clinically insignificant.

Removable Silicon Insertion Stiffeners for Neural Probes Using Polyethylene Glycol As a Biodissolvable Adhesive Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference. 2012 | Pubmed ID: 23366031 Flexible polymer probes are expected to enable extended interaction with neural tissue by minimizing damage from micromotion and reducing inflammatory tissue response. However, their flexibility prevents them from being easily inserted into the tissue. This paper describes an approach for temporarily attaching a silicon stiffener with biodissolvable polyethylene glycol (PEG) so that the stiffener can be released from the probe and extracted shortly after probe placement. A novel stiffener design with wicking channels, along with flip-chip technology, enable accurate alignment of the probe to the stiffener, as well as uniform distribution of the PEG adhesive. Insertion, extraction, and electrode function were tested in both agarose gel and a rat brain. Several geometric and material parameters were tested to minimize probe displacement during stiffener extraction. We demonstrated average probe displacement of 28 Â± 9 Âµm.

Optimization of Multi-layer Metal Neural Probe Design Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference. 2012 | Pubmed ID: 23367295 We present here a microfabrication process for multi-layer metal, multi-site, polymer-based neural probes. The process has been used to generate 1-, 2-, and 4-layer trace metal neural probes with highly uniform and reproducible electrode characteristics. Typically, increasing the number of metal layers is assumed to both reduce the width of the neural probes and minimize the injury and glial scarring caused at the implantation site. We show, however, that increasing the number of trace metal layers does not always result in the minimal probe cross-sectional area. A thorough design analysis reveals that the electrode size, along with other design parameters, have interacting effects on the probe cross-sectional area. Moreover, increasing the trace metal layers in the neural probes also increases the design and fabrication cost/time, as well as the likelihood of probe failure. Consequently, all of these factors must be considered when designing a multi-site, neural probe with the objective of minimizing tissue damage.

Polymer Neural Interface with Dual-sided Electrodes for Neural Stimulation and Recording Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference. 2012 | Pubmed ID: 23367296 We present here a demonstration of a dual-sided, 4-layer metal, polyimide-based electrode array suitable for neural stimulation and recording. The fabrication process outlined here utilizes simple polymer and metal deposition and etching steps, with no potentially harmful backside etches or long exposures to extremely toxic chemicals. These polyimide-based electrode arrays have been tested to ensure they are fully biocompatible and suitable for long-term implantation; their flexibility minimizes the injury and glial scarring that can occur at the implantation site. The creation of dual-side electrode arrays with more than two layers of trace metal enables the fabrication of neural probes with more electrodes without a significant increase in probe size. This allows for more stimulation/recording sites without inducing additional injury and glial scarring.

Cri Du Chat Syndrome: a Series of Five Cases Indian Journal of Pathology & Microbiology. Oct, 2012 | Pubmed ID: 23455788 The cri du chat syndrome (CdCS) is a chromosomal deletion syndrome associated with a partial deletion of the short (p) arm of chromosome 5. We describe five children who were diagnosed to have CdCS by conventional cytogenetic analysis. The deletion was at 5p15 in four patients, whereas the fifth had a larger, more proximal deletion at 5p14. Fluorescence in situ hybridization (FISH) analysis confirmed the deletion of the CdCS critical region at 5p15.2. All five children had global developmental delay and dysmorphism with microcephaly. The other clinical features were variable. Since the clinical diagnosis of CdCS may not always be evident because of the phenotypic heterogeneity, cytogenetic analysis is necessary to establish the diagnosis and confirm that the deletion involves the CdCS critical region. This will enable early intervention which plays an important role in improving the outcome.

Coordinated Cardiac Delivery: Reducing Mortality in High Risk Fetal Cardiac Lesions at the University of Mississippi Medical Center Journal of the Mississippi State Medical Association. Dec, 2012 | Pubmed ID: 23461044

Revitalization of the University of Mississippi Children's Heart Center: Report Card from the First 18 Months Journal of the Mississippi State Medical Association. Dec, 2012 | Pubmed ID: 23461045

Bronchial Artery Embolization Seminars in Interventional Radiology. Sep, 2012 | Pubmed ID: 23997406 Hemoptysis represents a significant clinical entity with high morbidity and potential mortality. Most hemorrhages from a bronchial source arise in the setting of chronic inflammatory diseases. Medical management (in terms of resuscitation and bronchoscopic interventions) and surgery have severe limitations in these patient populations. Embolization procedures represent the first-line treatment for hemoptysis arising from a bronchial arterial source. This article discusses anatomical and technical considerations, as well as outcomes and complications, in the setting of bronchial arterial embolization in the treatment of hemoptysis.

CT of Gallbladder Cancer and Its Mimics: a Pattern-based Approach Abdominal Imaging. Jun, 2013 | Pubmed ID: 22581235 On computed tomography (CT), gallbladder pathology may be detected incidentally or as the etiology of symptoms that prompted imaging. Accurate pathologic diagnosis can be challenging, however, due to overlapping appearances of malignant and benign gallbladder disease. This pictorial essay takes a pattern-based approach to CT of the gallbladder, to help the radiologist formulate the proper differential diagnosis.

Higher Volume Endovascular Stroke Centers Have Faster Times to Treatment, Higher Reperfusion Rates and Higher Rates of Good Clinical Outcomes Journal of Neurointerventional Surgery. Jul, 2013 | Pubmed ID: 22581925 Technological advances have helped to improve the efficiency of treating patients with large vessel occlusion in acute ischemic stroke. Unfortunately, the sequence of events prior to reperfusion may lead to significant treatment delays. This study sought to determine if high-volume (HV) centers were efficient at delivery of endovascular treatment approaches.

Frequencies of Obesity Susceptibility Alleles Among Ethnically and Racially Diverse Bariatric Patient Populations Surgery for Obesity and Related Diseases : Official Journal of the American Society for Bariatric Surgery. May-Jun, 2013 | Pubmed ID: 22695173 Genetic factors likely play a role in obesity and the outcomes after bariatric surgery. Single nucleotide polymorphisms in or near the insulin-induced gene 2 (INSIG-2), fat mass and obesity-associated gene (FTO), melanocortin 4 receptor gene (MC4R), and proprotein convertase subtilisn/kexin type 1 gene (PCSK-1) have been associated with class III obesity in whites. Minimal data are available regarding the genetic susceptibility to obesity in class III obese nonwhites, especially Hispanics. Our objective was to perform a comparative analysis of 4 common genetic variants (INSIG-2, FTO, MC4R, and PCSK-1) associated with obesity in a diverse population of bariatric surgery patients to determine whether a difference exists by ethnicity (white versus Hispanic). The setting of the study was 2 university hospitals in the United States.

Operative Treatment of Early Peri-prosthetic Femur Fractures Following Primary Total Hip Arthroplasty The Journal of Arthroplasty. Feb, 2013 | Pubmed ID: 22868075 The risk factors for and results of operatively treated peri-prosthetic femoral fractures sustained within 90 days following primary THA were evaluated. 5,313 consecutive THAs were reviewed and 32 (0.60%) fractures were identified which included 9 A(g), 2 B(1), 18 B(2), 1 B(3), and 2 A(g)/B(2) fractures. 19 (61%) patients sustained 23 complications including 9 greater trochanter non-unions, 2 femoral shaft non-unions, 3 patients with Brooker III HO, and 2 deep infections. 7 patients (23%) required a second operative procedure and one patient required a third. Peri-prosthetic fractures were associated with advancing age, female gender, developmental hip dysplasia, and cementless metaphyseal engaging components, particularly flat wedge tapers. Overall, operative treatment of acute peri-prosthetic fractures is associated with a high rate of complications (61%) and re-operation (23%).

Dye-enhanced Multimodal Confocal Imaging As a Novel Approach to Intraoperative Diagnosis of Brain Tumors Brain Pathology (Zurich, Switzerland). Jan, 2013 | Pubmed ID: 22882328 Intraoperative diagnosis plays an important role in accurate sampling of brain tumors, limiting the number of biopsies required and improving the distinction between brain and tumor. The goal of this study was to evaluate dye-enhanced multimodal confocal imaging for discriminating gliomas from nonglial brain tumors and from normal brain tissue for diagnostic use. We investigated a total of 37 samples including glioma (13), meningioma (7), metastatic tumors (9) and normal brain removed for nontumoral indications (8). Tissue was stained in 0.05â€‰mg/mL aqueous solution of methylene blue (MB) for 2-5 minutes and multimodal confocal images were acquired using a custom-built microscope. After imaging, tissue was formalin fixed and paraffin embedded for standard neuropathologic evaluation. Thirteen pathologists provided diagnoses based on the multimodal confocal images. The investigated tumor types exhibited distinctive and complimentary characteristics in both the reflectance and fluorescence responses. Images showed distinct morphological features similar to standard histology. Pathologists were able to distinguish gliomas from normal brain tissue and nonglial brain tumors, and to render diagnoses from the images in a manner comparable to haematoxylin and eosin (H&E) slides. These results confirm the feasibility of multimodal confocal imaging for intravital intraoperative diagnosis.

Bloom Syndrome: Report of Two Cases in Siblings International Journal of Dermatology. Aug, 2013 | Pubmed ID: 22998028

Is Mohs Micrographic Surgery More Effective Than Wide Local Excision for Treatment of Dermatofibrosarcoma Protuberans in Reducing Risk of Local Recurrence? A Critically Appraised Topic The British Journal of Dermatology. Jan, 2013 | Pubmed ID: 23013468

Outcome and Determinants of Mortality in 269 Patients with Combination Anti-tuberculosis Drug-induced Liver Injury Journal of Gastroenterology and Hepatology. Jan, 2013 | Pubmed ID: 23020522 Worldwide anti-tuberculosis (TB) drug-induced liver disease (DILI) is an important cause of hepatotoxicity, and drug-induced acute liver failure (ALF). Reported series on anti-TB DILI are limited by a mix of cases with mild transaminase elevation or adaptation. Our aim was to analyze the clinical features, laboratory characteristics, outcome, and determine predictors of 90-day mortality.

A Graph-based Recovery and Decomposition of Swanson's Hypothesis Using Semantic Predications Journal of Biomedical Informatics. Apr, 2013 | Pubmed ID: 23026233 This paper presents a methodology for recovering and decomposing Swanson's Raynaud Syndrome-Fish Oil hypothesis semi-automatically. The methodology leverages the semantics of assertions extracted from biomedical literature (called semantic predications) along with structured background knowledge and graph-based algorithms to semi-automatically capture the informative associations originally discovered manually by Swanson. Demonstrating that Swanson's manually intensive techniques can be undertaken semi-automatically, paves the way for fully automatic semantics-based hypothesis generation from scientific literature.

Intracranial Pressure Dose and Outcome in Traumatic Brain Injury Neurocritical Care. Feb, 2013 | Pubmed ID: 23055087 Detecting and treating elevated intracranial pressure (ICP) is a cornerstone of management in patients with severe traumatic brain injury. The aim of this study was to determine the association between area under the curve measurement of elevated ICP and clinical outcome.

Advanced Modality Imaging Evaluation in Acute Ischemic Stroke May Lead to Delayed Endovascular Reperfusion Therapy Without Improvement in Clinical Outcomes Journal of Neurointerventional Surgery. May, 2013 | Pubmed ID: 23076268 Advanced neuroimaging techniques may improve patient selection for endovascular stroke treatment but may also delay time to reperfusion. We studied the effect of advanced modality imaging with CT perfusion (CTP) or MRI compared with non-contrast CT (NCT) in a multicenter cohort.

Prevalence, Treatment, and Outcomes of Coexistent Ocular Surface Squamous Neoplasia and Pterygium Ophthalmology. Mar, 2013 | Pubmed ID: 23107578 The purpose of this study was to determine the prevalence of ocular surface squamous neoplasia (OSSN) coexisting with pterygia in South Florida and to study the treatment and related outcomes.

Validation of the Innocor Device for Noninvasive Measurement of Oxygen Consumption in Children and Adults Pediatric Cardiology. Apr, 2013 | Pubmed ID: 23108483 Outpatient measurements of oxygen consumption (VO2) and cardiac output (CO) are valuable in the management of pediatric cardiac disease. Current methods are inaccurate and cumbersome or require invasive procedures. New devices to measure these variables in adults have not been rigorously tested for children. The Innocor system uses a photoacoustic analyzer to measure gas content for noninvasive measurement of VO2 and CO. This study sought to validate Innocor-derived VO2 measurements in children and adults by comparing them against the gold standard Douglas bag method. Subjects were tested in an outpatient setting. Adaptations were made for pediatric patients based on weight. Resting VO2 measurements were obtained simultaneously by the Innocor system and Douglas bag during 3 min. The study enrolled 31 children (mean age, 12.2 years; range, 7-17 years, 17 girls) and 29 adults (mean age, 36.7 years; range, 19-57 years; 17 women). Strong correlation between the two techniques was seen for both the adults (R (2) = 0.88) and the children (R (2) = 0.82). The average discrepancy between the Innocor and Douglas bag measurements was 1.7 % (range, 0.6-19.1 %) for the adults, and 5.4 % (range, 0.1-32.2 %) for the children. The discrepancy was more than 15 % for 17 % of the adults and 22 % of the children, with the Innocor device tending to overestimate VO2 in children compared with the Douglas bag. This trend was not seen in adults. The Innocor system has excellent correlation with the Douglas bag and shows promise for noninvasive measurement of VO2 and CO in the school-age pediatric population.

Oxidative Modification of the Intestinal Mucus Layer is a Critical but Unrecognized Component of Trauma Hemorrhagic Shock-induced Gut Barrier Failure American Journal of Physiology. Gastrointestinal and Liver Physiology. Jan, 2013 | Pubmed ID: 23125158 Recent studies demonstrate that mechanisms underlying gut barrier failure include systemic processes and less studied luminal processes. We thus tested the hypothesis that mucus layer oxidation is a component of trauma/hemorrhagic shock-induced gut injury and dysfunction. Male Sprague-Dawley rats underwent trauma/hemorrhagic shock. Controls underwent trauma only. Mucus from the terminal 30 cm of the ileum was collected, processed, and analyzed for reactive nitrogen intermediates (RNI)-mediated damage, reactive oxygen species (ROS)-induced damage, and total antioxidant capacity. The distal ileum was stained to quantify the mucus layer; gut permeability was assessed physiologically. A time course study was conducted to determine the temporal sequence of mucus layer damage. The role of free radical-mediated damage to the gut barrier was investigated by the effect of the free radical scavenger dimethyl sulfoxide on trauma/hemorrhagic shock-induced changes on the mucus and on gut permeability. Trauma/hemorrhagic shock increased intestinal permeability, which was associated with evidence of loss of the unstirred mucus layer. These changes correlated with increased ROS- and RNI-mediated mucus damage and loss of mucus total antioxidant capacity. Based on the time course study, ROS-mediated mucus damage and loss of total antioxidant capacity were present immediately following shock, whereas RNI-mediated damage was delayed for 3 h. Dimethyl sulfoxide ameliorated gut barrier loss, ROS-mediated changes to the mucus layer, and loss of total antioxidant capacity. There was no change in RNI-induced changes to the mucus layer. These results support the hypothesis that trauma/hemorrhagic shock leads to mucus damage and gut dysfunction through the generation of free radical species.

Beneficial Effect of Subsequent Lesion Procedures After Nonresponse to Initial Cingulotomy for Severe, Treatment-refractory Obsessive-compulsive Disorder Neurosurgery. Feb, 2013 | Pubmed ID: 23147780 Anterior cingulotomy (AC) can be an effective therapy for patients with severe obsessive-compulsive disorder who are refractory to traditional medical therapy. For patients who do not respond to AC, the benefit of additional lesion procedures vs continued medical management remains unknown.

Bisphosphonates-related Osteonecrosis of the Jaws: a Preliminary Study of Salivary Interleukins Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. May, 2013 | Pubmed ID: 23157469 The aim of this preliminary study was analyze the possible alterations in some salivary interleukins, usually associated with the inflammatory processes.

Dynamic Multi-channel TMS with Reconfigurable Coil IEEE Transactions on Neural Systems and Rehabilitation Engineering : a Publication of the IEEE Engineering in Medicine and Biology Society. May, 2013 | Pubmed ID: 23193321 Investigations of the causal involvement of particular brain areas and interconnections in behavior require an external stimulation system with reasonable spatio-temporal resolution. Current transcranial magnetic stimulation (TMS) technology is limited to stimulating a single brain area once in a given trial. Here, we present a feasibility study for a novel TMS system based on multi-channel reconfigurable coils. With this hardware, researchers will be able to stimulate multiple brain sites in any temporal order in a trial. The system employs a wire-mesh coil, constructed using x- and y-directional wires. By varying the current direction and/or strength on each wire, we can configure the proposed mesh-wire coil into a standard loop coil and figure-eight coil of varying size. This provides maximum flexibility to the experimenter in that the location and extent of stimulation on the brain surface can be modified depending on experimental requirement. Moreover, one can dynamically and automatically modify the site(s) of stimulation several times within the span of seconds. By pre-storing various sequences of excitation patterns inside a control unit, one can explore the effect of dynamic TMS on behavior, in associative learning, and as rehabilitative therapy. Here, we present a computer simulation and bench experiments that show the feasibility of the dynamically-reconfigurable coil.

"I Just Wanted to Tell You That Loperamide WILL WORK": a Web-based Study of Extra-medical Use of Loperamide Drug and Alcohol Dependence. Jun, 2013 | Pubmed ID: 23201175 Many websites provide a means for individuals to share their experiences and knowledge about different drugs. Such User-Generated Content (UGC) can be a rich data source to study emerging drug use practices and trends. This study examined UGC on extra-medical use of loperamide among illicit opioid users.

Is Lower IQ in Children with Epilepsy Due to Lower Parental IQ? A Controlled Comparison Study Developmental Medicine and Child Neurology. Mar, 2013 | Pubmed ID: 23216381 The aim of this study was to determine the relationship between parent and child Full-scale IQ (FSIQ) in children with epilepsy and in typically developing comparison children and to examine parent-child IQ differences by epilepsy characteristics.

Limbic System Surgery for Treatment-refractory Obsessive-compulsive Disorder: a Prospective Long-term Follow-up of 64 Patients Journal of Neurosurgery. Mar, 2013 | Pubmed ID: 23240700 Obsessive-compulsive disorder (OCD) is a common and disabling psychiatric illness, and in a significant proportion of patients with OCD the disease is refractory to conventional pharmacotherapy and psychotherapy. For more than half a century, patients with severe, treatment-resistant OCD have been treated with stereotactic limbic system lesions, including dorsal anterior cingulotomy. The authors present their results describing the efficacy and durability of limbic system surgery for OCD, characterizing a large cohort of patients treated at a single institution with a mean follow-up of more than 5 years.

Long-term Impact of Integration of Household Water Treatment and Hygiene Promotion with Antenatal Services on Maternal Water Treatment and Hygiene Practices in Malawi The American Journal of Tropical Medicine and Hygiene. Feb, 2013 | Pubmed ID: 23243106 A clinic-based program to integrate antenatal services with distribution of hygiene kits including safe water storage containers, water treatment solution (brand name WaterGuard), soap, and hygiene education, was implemented in Malawi in 2007 and evaluated in 2010. We surveyed 389 participants at baseline in 2007, and found and surveyed 232 (60%) participants to assess water treatment, test stored drinking water for residual chlorine (an objective measure of treatment), and observe handwashing technique at follow-up in 2010. Program participants were more likely to know correct water treatment procedures (67% versus 36%; P < 0.0001), treat drinking water with WaterGuard (24% versus 2%; P < 0.0001), purchase and use WaterGuard (21% versus 1%; P < 0.001), and demonstrate correct handwashing technique (50% versus 21%; P < 0.001) at the three-year follow-up survey than at baseline. This antenatal-clinic-based program may have contributed to sustained water treatment and proper handwashing technique among program participants.

Clinical and Molecular Characterization of Patients with Gross Hypotonia and Impaired Lower Motor Neuron Function Indian Pediatrics. Jun, 2013 | Pubmed ID: 23255680 Spinal muscular atrophy (SMA) represents the second most common fatal autosomal recessive disorder after cystic fibrosis. Due to the high carrier frequency, the burden of this genetic disorder is very heavy in developing countries like India. The aim was to study the clinical and molecular characteristics of patients suspected with SMA. It was a cross sectional study of 105 cases from January 2008 to August 2012. Patients demographic and presenting features and PCR findings were noted. 65 (62%) cases had a confirmed diagnosis of SMA. Werdnig Hoffman disease (SMA type I) was the commonest variant seen in 34 (52.3%) children. Molecular analysis demonstrated deletion of both exon 7 and 8 of SMN1 gene in 83.1% of cases.

Measurement and Correction of Stimulated Echo Contamination in T2-based Iron Quantification Magnetic Resonance Imaging. Jun, 2013 | Pubmed ID: 23260394 The purpose of this study was to characterize the effects of stimulated echo contamination on MR-based iron measurement derived from quantitative T2 images and develop a method for retrospective correction. Two multiple spin-echo (MSE) pulse sequences were implemented with different amounts of stimulated echo contamination. Agarose-based phantoms were constructed that simulate the relaxation and susceptibility properties of tissue with different concentrations of dispersed (ferritin-like) and aggregated (hemosiderin-like) iron. Additionally, myocardial iron was assessed in nine human subjects with transfusion iron overload. These data were used to determine the influence of stimulated echoes on iron measurements made by an MR-based iron quantification model that can separately measure dispersed and aggregated iron. The study found that stimulated echo contamination caused an underestimation of dispersed (ferritin-like) iron and an overestimation of aggregated (hemosiderin-like) iron when applying this model. The relationship between the measurements made with and without stimulated echo appears to be linear. The findings suggest that while it is important to use MSE sequences with minimal stimulated echo in T2-based iron quantification, it appears that data acquired with sub-optimal sequences can be retrospectively corrected using the methodology described here.

Circulating Tumor Cells: Personalized Medicine in Interventional Oncology? Journal of Vascular and Interventional Radiology : JVIR. Feb, 2013 | Pubmed ID: 23265726 Innovative technologic advancements have expanded the ability of interventional radiologists to capture and visualize directly tumor cells that have intravasated into the circulation. The detection of these circulating tumor cells (CTCs) is revolutionizing the understanding of the pathogenesis of metastasis and is paving the way for exquisitely sensitive techniques to detect malignancy, monitor recurrence, and prognosticate outcomes. In this review, the prevailing theories on the pathobiology of metastasis and the tools that have been developed to investigate CTCs are summarized. The tremendous impact CTCs are likely to have in oncology is discussed, with particular emphasis on their relevance to interventional oncology.

Super Flexion Position for Difficult Speculum Examination International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. Apr, 2013 | Pubmed ID: 23273889

HIV Infection Deregulates Innate Immunity to Malaria Despite Combination Antiretroviral Therapy AIDS (London, England). Jan, 2013 | Pubmed ID: 23291537 Malaria and HIV-1 adversely interact, with HIV-positive individuals suffering higher parasite burdens and worse clinical outcomes. However, the mechanisms underlying these disease interactions are unclear. We hypothesized that HIV coinfection impairs the innate immune response to malaria, and that combination antiretroviral therapy (cART) may restore this response. Our aim was to examine the innate inflammatory response of natural killer (NK), natural killer T (NKT), and Î³Î´ T-cells isolated from the peripheral blood of HIV-infected therapy-naive donors to malaria parasites, and determine the effect of cART on these responses.

Neuroresuscitation--not to Be Taken Lying Down Journal of Critical Care. Apr, 2013 | Pubmed ID: 23294580

Exfoliation Syndrome: New Genetic and Pathophysiologic Insights Current Opinion in Ophthalmology. Mar, 2013 | Pubmed ID: 23299249 Exfoliation syndrome is the most common identifiable cause of glaucoma in the world. It has been associated with many ocular problems, such as secondary open angle glaucoma, corneal dysfunction, cataract, and zonular weakness, and may have systemic manifestations as well. This review focuses on recent genetic and pathophysiologic discoveries in the disease process.

Prenatal Dolichocephaly: Sign of Trouble? -A Variant of Miller-Dieker Syndrome Fetal and Pediatric Pathology. Jul, 2013 | Pubmed ID: 23301919 Neuroimaging and molecular cytogenetics were used to ascertain the cause of disability in a case. The case was diagnosed to be a variant of Miller-Dieker syndrome (MDS). Retrospective analysis showed a prenatal scan reporting dolichocephaly. We evaluated dolichocephaly, the name associated with a nonsynostotic cause to be a physiological variant having no prognostic value, to that of a similar synostotic or secondary to a neurological disorder cause, with prognostic significance. The report confirmed early craniosynostosis in cases suspected with a neurological disorder and also on an important criterion in molecular testing strategy in cases suspected with MDS.

Cystoid Macular Edema Associated with Fingolimod Use for Multiple Sclerosis JAMA Ophthalmology. Jan, 2013 | Pubmed ID: 23307220

HIV Infection Deregulates Tim-3 Expression on Innate Cells: Combination Antiretroviral Therapy Results in Partial Restoration Journal of Acquired Immune Deficiency Syndromes (1999). Jun, 2013 | Pubmed ID: 23314411 The Tim-3 receptor has been implicated as a negative regulator of adaptive immune responses and has been linked to T-cell dysfunction in chronic viral infections, such as HIV. Blocking Tim-3 has been proposed as a potential therapeutic intervention in HIV infection. However, a more detailed characterization of Tim-3 expression in the presence of HIV is required before such strategies can be considered.

Sound-induced Perturbations of the Brain Network in Non-REM Sleep, and Network Oscillations in Wake Psychophysiology. Mar, 2013 | Pubmed ID: 23316945 During sleep, the brain network processes sensory stimuli without awareness. Stimulation must affect differently brain networks in sleep versus wake, but these differences have yet to be quantified. We recorded cortical activity in stage 2 (SII) sleep and wake using EEG while a tone was intermittently played. Zero-lag correlation measured input to pairs of sensors in the network; cross-correlation and phase-lag index measured pairwise corticocortical connectivity. Our analysis revealed that under baseline conditions, the cortical network, in particular the central regions of the frontoparietal cortex, interact at a characteristic latency of 50 ms, but only during wake, not sleep. Nonsalient auditory stimulation causes far greater perturbation of connectivity from baseline in sleep than wake, both in the response to common input and corticocortical connectivity. The findings have key implications for sensory processing.

Clinical Predictors and Management of Hemorrhagic Transformation Current Treatment Options in Neurology. Apr, 2013 | Pubmed ID: 23325069 Hemorrhagic Transformation (HT) has been well recognized as a common cause of hemorrhage in ischemic stroke patients. Though this complication may occur independently, it has been particularly dreaded in the post rTPA patient and thus has been the focus for analysis of multiple thrombolytic trials. This review examines the effect of different clinical predictors for hemorrhagic transformation and summarizes pertinent clinical trials, with a focus on the rational for design of future studies. Although currently there are no official guidelines for the acute management of HT per se, based upon review of the literature regarding pertinent clinical predictors herein, an innovative approach for the acute management of the HT patient is proposed.

Impact of Antiretroviral Therapy Duration and Intensification on Isolated Shedding of HIV-1 RNA in Semen The Journal of Infectious Diseases. Apr, 2013 | Pubmed ID: 23329849 Effective antiretroviral therapy (ART) dramatically reduces human immunodeficiency virus (HIV) transmission. However, isolated shedding of HIV type 1 (HIV-1) in semen (IHS) can occur in the absence of detectable viremia or genital infections. We hypothesized that ART intensification with medications active in semen might prevent IHS.

Randomized Phase II Study of Cetuximab and Bevacizumab in Combination with Two Regimens of Paclitaxel and Carboplatin in Chemonaive Patients with Stage IIIB/IV Non-small-cell Lung Cancer Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer. Mar, 2013 | Pubmed ID: 23370316 We conducted a phase II study of dual-agent monoclonal antibody therapy consisting of cetuximab and bevacizumab in combination with paclitaxel and carboplatin chemotherapy in non-small-cell lung cancer.

Fluorochrome-functionalized Nanoparticles for Imaging DNA in Biological Systems ACS Nano. Mar, 2013 | Pubmed ID: 23373524 Attaching DNA binding fluorochromes to nanoparticles (NPs) provides a way of obtaining NPs that bind to DNA through fluorochrome mediated interactions. To obtain a nanoparticle (NP) that bound to the DNA in biological systems, we attached the DNA binding fluorochrome, TO-PRO 1 (TO), to the surface of the Feraheme (FH) NP, to obtain a fluorochrome-functionalized NP denoted TO-FH. When reacted with DNA in vitro, TO-FH formed microaggregates that were characterized by fluorescence, light scattering, and T2 changes. The formation of DNA/TO-FH microaggregates was also characterized by AFM, with microaggregates exhibiting a median size of 200 nm, and consisting of DNA and multiple TO-FH NPs whose individual diameters were only 25-35 nm. TO-FH failed to bind normal cells in culture, but treatment with chemotherapeutic agents or detergents yielded necrotic cells that bound TO-FH and vital fluorochromes similarly. The uptake of TO-FH by HT-29 xenografts (treated with 5-FU and oxaliplatin) was evident by surface fluorescence and MRI. Attaching multiple DNA binding fluorochromes to magnetic nanoparticles provides a way of generating DNA binding NPs that can be used to detect DNA detection by microaggregate formation in vitro, for imaging the DNA of necrotic cells in culture, and for imaging the DNA of a tumor treated with a chemotherapeutic agent. Fluorochrome functionalized NPs are a multimodal (magnetic and fluorescent), highly multivalent (n â‰ˆ 10 fluorochromes/NP) nanomaterials useful for imaging the DNA of biological systems.

Enteral Feeding in Head and Neck Cancer Patients at a UK Cancer Centre Journal of Human Nutrition and Dietetics : the Official Journal of the British Dietetic Association. Oct, 2013 | Pubmed ID: 23379517 Patients undergoing radiotherapy or chemoradiotherapy treatment for head and neck cancer have an increased risk of malnutrition, and may require enteral feeding via nasogastric or gastrostomy tube. The aim of this audit was to examine current enteral feeding practice, mortality, morbidity and 6-month outcome data of head and neck cancer patients receiving radical (chemo)radiotherapy at a regional cancer centre and to compare the results with a regional head and neck cancer gastrostomy audit.

Factors Affecting Successful Localization of the Central Sulcus Using the Somatosensory Evoked Potential Phase Reversal Technique Neurosurgery. May, 2013 | Pubmed ID: 23381491 Perirolandic surgery is associated with an increased risk of postoperative neurological deficit that can be reduced by accurate recognition of the location of sensorimotor cortex. The median somatosensory evoked potential (MSSEP) phase reversal technique (PRT) reliably identifies the central sulcus (CS) intraoperatively, but does require additional surgical time. Awareness of factors that lengthen the time required for MSSEP PRT has important implications for surgical planning.

Predictors of Cranioplasty Complications in Stroke and Trauma Patients Journal of Neurosurgery. Apr, 2013 | Pubmed ID: 23394335 Decompressive craniectomy mandates subsequent cranioplasty. Complications of cranioplasty may be independent of the initial craniectomy, or they may be contingent upon the craniectomy. Authors of this study aimed to identify surgery- and patient-specific risk factors related to the development of surgical site infection and other complications following cranioplasty.

Neurological Surgery: the Influence of Physical and Mental Demands on Humans Performing Complex Operations Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. Mar, 2013 | Pubmed ID: 23394875 Performing neurological surgery is an inherently demanding task on the human body, both physically and mentally. Neurosurgeons routinely perform "high stakes" operations in the setting of mental and physical fatigue. These conditions may be not only the result of demanding operations, but also influential to their outcome. Similar to other performance-based endurance activities, training is paramount to successful outcomes. The inflection point, where training reaches the point of diminishing returns, is intensely debated. For the neurosurgeon, this point must be exploited to the maximum, as patients require both the best-trained and best-performing surgeon. In this review, we explore the delicate balance of training and performance, as well as some routinely used adjuncts to improve human performance.

Diagnostic Dilemma in Overlapping Congenital Syndromes Indian Pediatrics. Jan, 2013 | Pubmed ID: 23396793

Dosage Changes of MED13L Further Delineate Its Role in Congenital Heart Defects and Intellectual Disability European Journal of Human Genetics : EJHG. Oct, 2013 | Pubmed ID: 23403903 A chromosomal balanced translocation disrupting the MED13L (Mediator complex subunit13-like) gene, encoding a subunit of the Mediator complex, was previously associated with transposition of the great arteries (TGA) and intellectual disability (ID), and led to the identification of missense mutations in three patients with isolated TGA. Recently, a homozygous missense mutation in MED13L was found in two siblings with non-syndromic ID from a consanguineous family. Here, we describe for the first time, three patients with copy number changes affecting MED13L and delineate a recognizable MED13L haploinsufficiency syndrome. Using high resolution molecular karyotyping, we identified two intragenic de novo frameshift deletions, likely resulting in haploinsufficiency, in two patients with a similar phenotype of hypotonia, moderate ID, conotruncal heart defect and facial anomalies. In both, Sanger sequencing of MED13L did not reveal any pathogenic mutation and exome sequencing in one patient showed no evidence for a non-allelic second hit. A further patient with hypotonia, learning difficulties and perimembranous VSD showed a 1â€‰Mb de novo triplication in 12q24.2, including MED13L and MAP1LC3B2. Our findings show that MED13L haploinsufficiency in contrast to the previously observed missense mutations cause a distinct syndromic phenotype. Additionally, a MED13L copy number gain results in a milder phenotype. The clinical features suggesting a neurocristopathy may be explained by animal model studies indicating involvement of the Mediator complex subunit 13 in neural crest induction.

Authors' Reply: Confounding by Indication in Retrospective Studies of Intracerebral Hemorrhage: Antiepileptic Treatment and Mortality Neurocritical Care. Apr, 2013 | Pubmed ID: 23408339

Functional Assays of Local Connectivity in the Somatosensory Cortex of Individuals with Autism Autism Research : Official Journal of the International Society for Autism Research. Jun, 2013 | Pubmed ID: 23427110 Emerging evidence for differences between individuals with autism spectrum disorder (ASD) and neurotypical (NT) individuals in somatic processing and brain response to touch suggests somatosensory cortex as a promising substrate for elucidating differences in functional brain connectivity between individuals with and without autism. Signals from adjacent digits project to neighboring locations or representations in somatosensory cortex. When a digit is stimulated, i.e. touched, its representation in cortex is directly activated; local intracortical connections indirectly activate nonprimary cortical representations corresponding to adjacent digits. The response of the nonprimary cortical representations is thus a proxy for connection strength. Local overconnectivity in autism implies that the nonprimary/primary response ratios of the ASD group will be higher than those of the NT group. D1 and D2 of the dominant hand of the participant were individually stimulated while we recorded neural responses using magnetoencephalography. The cortical representations of D1 and D2 (somatosensory-evoked fields) were computed from the ensemble-averaged data using (a) dipole model fits and (b) singular value decomposition. Individual adjacent/primary response ratios were measured, and group response ratio data were fitted with straight lines. Local overconnectivity in autism implies steeper ASD vs. NT group slopes. Our findings did not support local overconnectivity. Slopes were found to be significantly shallower for the ASD group than the NT group. Our findings support the idea of local underconnectivity in the somatosensory cortex of the brains of individuals with ASD.

The Crohn's Disease Activity Index (CDAI) is Similarly Elevated in Patients with Crohn's Disease and in Patients with Irritable Bowel Syndrome Alimentary Pharmacology & Therapeutics. Apr, 2013 | Pubmed ID: 23432394 While the Crohn's disease activity index (CDAI) is the gold standard for defining clinical endpoints in Crohn's disease (Crohn's) clinical trials, its ability to distinguish symptoms due to inflammation from those that are non-inflammatory has been questioned.

Acetabular Bone Loss in Revision Total Hip Arthroplasty: Evaluation and Management The Journal of the American Academy of Orthopaedic Surgeons. Mar, 2013 | Pubmed ID: 23457063 As the number of primary total hip arthroplasty (THA) procedures performed continues to rise, the burden of revision THA procedures is also expected to increase. Proper evaluation and management of acetabular bone loss at the time of revision surgery will be an increasing challenge facing orthopaedic surgeons. Proper preoperative patient assessment and detailed preoperative planning are essential in obtaining a good clinical result. Appropriate radiographs are critical in assessing acetabular bone loss, and specific classification schemes can identify bone loss patterns and guide available treatment options. Treatment options include impaction grafting and cementation of the acetabulum, noncemented hemispheric acetabular reconstruction, structural allograft reconstruction, noncemented reconstruction with modular porous metal augments, ring and cage reconstruction, oblong cup reconstruction, cup-cage reconstruction, and triflange reconstruction.

Diabetic Retinopathy and VEGF The Open Ophthalmology Journal. 2013 | Pubmed ID: 23459241 Diabetic retinopathy remains the leading vascular-associated cause of blindness throughout the world. Its treatment requires a multidisciplinary interventional approach at both systemic and local levels. Current management includes laser photocoagulation, intravitreal steroids, and anti-vascular endothelial growth factor (VEGF) treatment along with systemic blood sugar control. Anti-VEGF therapies, which are less destructive and safer than laser treatments, are being explored as primary therapy for the management of vision-threatening complications of diabetic retinopathy such as diabetic macular edema (DME). This review provides comprehensive information related to VEGF and describes its role in the pathogenesis of diabetic retinopathy, and in addition, examines the mechanisms of action for different antiangiogenic agents in relation to the management of this disease. Medline (Pubmed) searches were carried out with keywords "VEGF", "diabetic retinopathy", and "diabetes" without any year limitation to review relevant manuscripts used for this article.

Induced and Sustained Hypernatremia for the Prevention and Treatment of Cerebral Edema Following Brain Injury Neurocritical Care. Oct, 2013 | Pubmed ID: 23468135 Cerebral edema develops in response to and as a result of a variety of neurologic insults such as ischemic stroke, traumatic brain injury, and tumor. It deforms brain tissue, resulting in localized mass effect and increase in intracranial pressure (ICP) that are associated with a high rate of morbidity and mortality. When administered in bolus form, hyperosmolar agents such as mannitol and hypertonic saline have been shown to reduce total brain water content and decrease ICP, and are currently the mainstays of pharmacological treatment. However, surprisingly, little is known about the increasingly common clinical practice of inducing a state of sustained hypernatremia. Herein, we review the available studies employing sustained hyperosmolar therapy to induce hypernatremia for the prevention and/or treatment of cerebral edema. Insufficient evidence exists to recommend pharmacologic induction of hypernatremia as a treatment for cerebral edema. The strategy of vigilant avoidance of hyponatremia is currently a safer, potentially more efficacious paradigm.

Effect of Radial Versus Femoral Access on Radiation Dose and the Importance of Procedural Volume: a Substudy of the Multicenter Randomized RIVAL Trial JACC. Cardiovascular Interventions. Mar, 2013 | Pubmed ID: 23517837 The authors sought to compare the radiation dose between radial and femoral access.

Outcome of Total Hip Arthroplasty As a Salvage Procedure for Failed Infected Internal Fixation of Hip Fractures Indian Journal of Orthopaedics. Jan, 2013 | Pubmed ID: 23533069 Failed infected internal fixation produces significant pain and functional disability. In infected internal fixation of hip fractures with partial or complete head destruction, total hip arthroplasty (THA) can be technically challenging; however, it restores hip biomechanics. The present study is to evaluate the results and assess the complications of THA following failed infected internal fixation of these fractures.

Vasectomy Demographics and Postvasectomy Desire for Future Children: Results from a Contemporary National Survey Fertility and Sterility. Jun, 2013 | Pubmed ID: 23541407 To describe the longitudinal demographics and family planning attitudes of vasectomized men with the use of the National Survey for Family Growth (NSFG).

Systematic Review: the Quality of the Scientific Evidence and Conflicts of Interest in International Inflammatory Bowel Disease Practice Guidelines Alimentary Pharmacology & Therapeutics. May, 2013 | Pubmed ID: 23550536 Guidelines published by the international gastroenterology societies establish standards of care and seek to improve patient outcomes.

Light-induced Tryptophan Radical Generation in a Click Modular Assembly of a Sensitiser-tryptophan Residue Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology. Jun, 2013 | Pubmed ID: 23558787 Click chemistry was used as an efficient method to covalently attach a chromophore to an amino acid. Such easily prepared model systems allow for time-resolved studies of one-electron oxidation reactions by the excitation of the chromophore by a laser flash. The model complex ruthenium-tryptophan (Ru-Trp) has been synthesised and studied for its photophysical and electrochemical properties. Despite a small driving force of less than 100 meV, excitation with a laser flash results in fast internal electron transfer leading to the formation of the protonated radical (TrpË™H(+)). At neutral pH electron transfer is followed by deprotonation to form the neutral TrpË™ radical with the rate depending on the concentration of water acting as the proton acceptor. The formation of the tryptophan radical was confirmed by EPR.

Vaginal Hysterectomy in Women with a History of 2 or More Cesarean Deliveries International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. Jul, 2013 | Pubmed ID: 23570749 To perform vaginal hysterectomy (VH) safely in women with a history of 2 or more cesarean deliveries (CDs).

Randomized, Double-masked, Placebo-controlled Study to Assess the Ocular Safety of Mirabegron in Healthy Volunteers Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics. Sep, 2013 | Pubmed ID: 23586728 Abstract Purpose: This study assessed the effect of mirabegron on ocular safety in healthy volunteers. Methods: This was an 8-week, randomized, double-masked, placebo-controlled study. Participants: Consenting adults aged â‰¥18 years with a normal intraocular pressure (IOP, â‰¥10 to â‰¤21â€‰mmHg) were eligible to enter the study. Of the 321 randomized subjects, 305 completed the study. Subjects were randomized 1:1 to a supratherapeutic dose of oral mirabegron 100â€‰mg or placebo once daily for 56 days. The IOP was measured at screening, baseline, day 10, and day 56/end of treatment using Goldmann applanation tonometry. Visual acuity and biomicroscopy were also evaluated. The primary endpoint was the mean change from baseline in the IOP at 56 days or end of treatment with mirabegron versus placebo. Secondary outcome variables included change from baseline to day 10 in the IOP, and increases in the IOP of â‰¥6â€‰mmHg and â‰¥10â€‰mmHg in either eye from baseline to day 10 and day 56. Results: The mean (standard error, SE) IOP at baseline was 15.3 (0.16) mmHg for mirabegron and 15.4 (0.16) mmHg for placebo; values at day 56 were 15.0 (0.16) mmHg and 15.2 (0.17) mmHg, respectively. The adjusted mean IOP change from baseline to day 56 was -0.3â€‰mmHg for mirabegron and -0.2â€‰mmHg for placebo (-0.1â€‰mmHg difference [95% confidence interval, CI, -0.4 to 0.3]). For the primary endpoint, mirabegron was noninferior to placebo, based on the prespecified limit of 1.5â€‰mmHg. No statistically significant treatment effects on the IOP were seen at day 10. No subject discontinued due to increased IOP. Clinically significant increases from baseline in the IOP occurred rarely and only with placebo treatment. Changes in the visual acuity and biomicroscopy were not suggestive of a mirabegron effect. No treatment-emergent adverse event (AE) of glaucoma was reported. Conclusions: Mirabegron 100â€‰mg orally once daily for 8 weeks of treatment does not increase the IOP, and was generally safe and well tolerated.

Hemodialysis for the Treatment of Pulmonary Hemorrhage from Dabigatran Overdose American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. Sep, 2013 | Pubmed ID: 23597859 Dabigatran is an oral direct thrombin inhibitor indicated for thromboembolism prophylaxis in patients with nonvalvular atrial fibrillation. Since its approval in the United States in 2010, dabigatran-associated hemorrhages have garnered much attention because bleeding rates were higher than initially expected. Additionally, reversing anticoagulation remains challenging. Traditional modes of reversing warfarin-associated coagulopathies are ineffective in reversing anticoagulation from dabigatran. Although hemodialysis is proposed as a method to accelerate dabigatran elimination, evidence supporting its clinical utility remains unproved. We report the case of an 80-year-old man who presented with worsening hemoptysis in the setting of unintentional ingestion of excess dabigatran. Despite transfusion of 2 units of fresh frozen plasma, he continued to bleed, although his international normalized ratio improved from 8.8 to 7.2. He underwent hemodialysis, and serum dabigatran concentration decreased from 1,100 to 18 ng/mL over 4 hours, with an initial extraction ratio of 0.97 and blood clearance of 291 mL/min. Although his serum dabigatran concentration rebounded to 100 ng/mL 20 minutes after the cessation of dialysis, his bleeding stopped and he improved clinically. Hemorrhage in the setting of dabigatran anticoagulation remains a therapeutic predicament. Hemodialysis may play an adjunct role in accelerating the elimination of dabigatran in bleeding patients.

Studying Task-related Activity of Individual Neurons in the Human Brain Nature Protocols. May, 2013 | Pubmed ID: 23598445 Single-neuronal studies remain the gold standard for studying brain function. Here we describe a protocol for studying task-related single-neuronal activity in human subjects during neurosurgical procedures involving microelectrode recordings. This protocol has two phases: a preoperative phase and an intraoperative phase. During the preoperative phase, we discuss informed consent, equipment setup and behavioral testing. During the intraoperative phase, we discuss the procedure for microelectrode recordings. Because patients are often awake during these procedures, this protocol can be performed in conjunction with behavioral tasks for studying a variety of cognitive functions. We describe the protocol in detail and provide two examples of expected results. In addition, we discuss the potential difficulties and pitfalls related to intraoperative studies. This protocol takes âˆ¼1.5 h to complete.

Bladder Separation at Abdominal Hysterectomy International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. Aug, 2013 | Pubmed ID: 23601437

Retinal Nerve Fibre Layer Imaging: Comparison of Cirrus Optical Coherence Tomography and Heidelberg Retinal Tomograph 3 Clinical & Experimental Ophthalmology. Apr, 2013 | Pubmed ID: 23601764 BACKGROUND: The propose of this study was to analyze the relationship between retinal nerve fibre layer (RNFL) thickness measured by spectral domain optical coherence tomography and confocal scanning laser ophthalmoscope. DESIGN: Prospective, cross-sectional study. Hospital setting. PARTICIPANTS: One hundred seventy-three subjects (85 glaucoma and 88 normal subjects). METHODS: One eye from each individual was selected randomly for RNFLT imaging by the spectral domain Cirrus OCT and HRT3. MAIN OUTCOME MEASURES: Global RNFL thickness and measurements at the four quadrants around the optic disc were analyzed and compared for differences, agreement of the categorical classification, diagnostic sensitivities and specificities and the area under the receiver operating characteristic curves (AUC). RESULTS: RNFL thickness as determined by HRT3 were significantly thicker than measurements done by Cirrus OCT (respectively in Î¼m, for global thickness: 200.0Â±87.2 and 80.7Â±14.7, for temporal quadrant: 75.3Â±31.9 and 59.1Â±13.8, for superior quadrant 223.2Â±128.4 and 97.7Â±20.9, for nasal quadrant 208.0Â±102.9 and 66.8Â±11.8, and for inferior quadrant 224.4Â±116.9 and 99.1Â±26.6, for all P

(18)F-FDG PET/CT Imaging of Metastatic Atypical Fibroxanthoma Clinical Nuclear Medicine. Jun, 2013 | Pubmed ID: 23603591 We report the F-FDG PET/CT appearance of a metastatic biopsy-proven malignant fibroxanthoma of the ankle. A 41-year-old female patient with a history of scleroderma presented with a fungating mass in the left ankle. Shave biopsy of the overlying skin showed atypical fibroxanthoma (AFX). Staging FDG PET/CT demonstrated a hypermetabolic exophytic soft tissue mass in the left ankle with local extension to bone and widespread metastatic disease including pulmonary parenchyma, nodes, bone marrow, and skeletal muscle. While rare, knowledge of the potential aggressive nature of AFX is important for accurate diagnosis.

Reporters for the Analysis of N-glycosylation in Candida Albicans Fungal Genetics and Biology : FG & B. Jul, 2013 | Pubmed ID: 23608318 A large proportion of Candida albicans cell surface proteins are decorated post-translationally by glycosylation. Indeed N-glycosylation is critical for cell wall biogenesis in this major fungal pathogen and for its interactions with host cells. A detailed understanding of N-glycosylation will yield deeper insights into host-pathogen interactions. However, the analysis of N-glycosylation is extremely challenging because of the complexity and heterogeneity of these structures. Therefore, in an attempt to reduce this complexity and facilitate the analysis of N-glycosylation, we have developed new synthetic C. albicans reporters that carry a single N-linked glycosylation site derived from Saccharomyces cerevisiae Suc2. These glycosylation reporters, which carry C.albicans Hex1 or Sap2 signal sequences plus carboxy-terminal FLAGâ‚ƒ and Hisâ‚† tags, were expressed in C.albicans from the ACT1 promoter. The reporter proteins were successfully secreted and hyperglycosylated by C.albicans cells, and their outer chain glycosylation was dependent on Och1 and Pmr1, which are required for N-mannan synthesis, but not on Mnt1 and Mnt2 which are only required for O-mannosylation. These reporters are useful tools for the experimental dissection of N-glycosylation and other related processes in C.albicans, such as secretion.

High-throughput Screening for the Development of a Monoclonal Antibody Affinity Precipitation Step Using ELP-z Stimuli Responsive Biopolymers Biotechnology and Bioengineering. Oct, 2013 | Pubmed ID: 23616271 This study provides a detailed investigation into the performance of a stimuli responsive ELP-Z based process for monoclonal antibody (mAb) affinity precipitation. A multidimensional high-throughput screening (HTS) protocol was developed and employed to investigate the effects of a variety of operating conditions on mAb yield and aggregation during the process. Precipitation efficiency of ELP-Z in the absence of mAb was first determined as a function of temperature and sodium sulfate concentration and conditions producing high yields were identified. HTS was then employed to determine appropriate conditions for the initial capture and co-precipitation of mAbs at high yields using ELP-Z. mAb elution from ELP-Z was then examined using HTS and the mAb yields and aggregate content of the overall process were determined. It was observed that mAb aggregation was sensitive primarily to the elution conditions and that this behavior was antibody specific and a strong function of operating temperature and elution pH. Importantly, for both mAbs examined in this study, the results indicated that room temperature operation and appropriate elution pH could be readily employed to produce both high mAb yields and low aggregate content using this approach. This study demonstrates the ability of ELP-Z based affinity precipitation for mAb purification and shows that HTS can be successfully employed to rapidly develop a robust and high yield process. Biotechnol. Bioeng. 2013;110: 2664-2676. Â© 2013 Wiley Periodicals, Inc.

Differential Linear Scan Voltammetry: Analytical Performance in Comparison with Pulsed Voltammetry Techniques Analytical and Bioanalytical Chemistry. Jun, 2013 | Pubmed ID: 23624955 We report here on differential linear scan voltammetry, DLSV, that combines the working principles of linear scan voltammetry, LSV, and the numerous existing pulsed voltammetry techniques. DLSV preserves the information from continuous interrogation in voltage and high accuracy that LSV provides about electrochemical processes, and the much better sensitivity of differential pulsed techniques. DLSV also minimizes the background current compared to both LSV and pulsed voltammetry. An early version of DLSV, derivative stationary electrode polarography, DSEP, had been proposed in the 1960s but soon abandoned in favor of the emerging differential pulsed techniques. Relative to DSEP, DLSV takes advantage of the flexibility of discrete smoothing differentiation that was not available to early investigators. Also, DSEP had been explored in pure solutions and with reversible electrochemical reactions. DLSV is tested in this work in more challenging experimental contexts: the measurement of oxygen with a carbon fiber microelectrode in buffer, and with a gold microdisc electrode exposed to a live biological preparation. This work compares the analytical performance of DLSV and square wave voltammetry, the most popular pulsed voltammetry technique.

Decompensated Cirrhotics Have Slower Intestinal Transit Times As Compared With Compensated Cirrhotics and Healthy Controls Journal of Clinical Gastroenterology. May, 2013 | Pubmed ID: 23632359 BACKGROUND:: Altered small intestinal motility in cirrhotics may play a major role in the development of bacterial translocation (BT) by leading to small intestinal bacterial overgrowth. BT has been implicated in the development of several complications including spontaneous bacterial peritonitis, esophageal variceal hemorrhage, and hepatorenal syndrome. Prior studies using antroduodenal manometry to evaluate intestinal motility have shown discrepancies regarding the relationship between dysmotility and the severity of cirrhosis. OBJECTIVES:: (1) To characterize the frequency of small bowel motility disturbances in cirrhotic patients using a wireless motility capsule (SmartPill); (2) To assess the relationship of intestinal dysmotility with liver disease severity and cirrhosis complications; and (3) To compare intestinal transit times and motility indices among cirrhotics and healthy controls. METHODS:: We conducted a prospective study of 20 patients with cirrhosis (10 compensated, 10 decompensated) who were recruited from Yale New Haven Hospital and Hepatology clinics (February 2011 to July 2011). All patients underwent and completed SmartPill studies. Intestinal transit times were calculated, analyzed, and compared among compensated versus decompensated cirrhotics versus historical, healthy controls. Intestinal transit delays/motility indices were correlated with disease severity and complications. RESULTS:: Decompensated cirrhotics had significantly longer small bowel transit times (SBTT) as compared with compensated cirrhotics (6.17 vs. 3.56 h, P=0.036). There was a significant correlation (r=0.77, P=0.0003) between SBTT and cirrhosis severity as assessed by Child-Pugh score. There were no statistical differences noted between the groups for gastric or colonic transit times, although there was a trend toward prolonged transit throughout the gut in decompensated. Cirrhotics with spontaneous bacterial peritonitis and ascites also had significantly longer SBTT as compared with those without. CONCLUSIONS:: This study demonstrates that decompensated cirrhotics have slower intestinal transit times as compared with compensated cirrhotics and healthy controls. Additional prospective studies are needed to further characterize dysmotility in cirrhotics and its relationship to complications related to BT. This would aid in the identification of patients at risk for developing severe complications and who may benefit from prophylactic prokinetic and/or antimicrobial therapy.

Decoupling the Function of Hox and Shh in Developing Limb Reveals Multiple Inputs of Hox Genes on Limb Growth Development (Cambridge, England). May, 2013 | Pubmed ID: 23633510 Limb development relies on an exquisite coordination between growth and patterning, but the underlying mechanisms remain elusive. Anterior-posterior and proximal-distal specification initiates in early limb bud concomitantly with the proliferative expansion of limb cells. Previous studies have shown that limb bud growth initially relies on fibroblast growth factors (FGFs) produced in the apical ectodermal ridge (AER-FGFs), the maintenance of which relies on a positive-feedback loop involving sonic hedgehog (Shh) and the BMP antagonist gremlin 1 (Grem1). The positive cross-regulation between Shh and the HoxA and HoxD clustered genes identified an indirect effect of Hox genes on the maintenance of AER-FGFs but the respective function of Shh and Hox genes in this process remains unknown. Here, by uncoupling Hox and Shh function, we show that HoxA and HoxD genes are required for proper AER-FGFs expression, independently of their function in controlling Shh expression. In addition, we provide evidence that the Hox-dependent control of AER-FGF expression is achieved through the regulation of key mesenchymal signals, namely Grem1 and Fgf10, ensuring proper epithelial-mesenchymal interactions. Notably, HoxA and HoxD genes contribute to both the initial activation of Grem1 and the subsequent anterior expansion of its expression domain. We propose that the intricate interactions between Hox genes and the FGF and Shh signaling pathways act as a molecular network that ensures proper limb bud growth and patterning, probably contributing to the coordination of these two processes.

Ureteral Stenting and Retrograde Pyelography in the Office: Clinical Outcomes, Cost Effectiveness, and Time Savings Journal of Endourology / Endourological Society. May, 2013 | Pubmed ID: 23638674 To examine the clinical outcomes and cost-effectiveness of endourologic procedures performed in the office using standard fluoroscopy and topical anesthesia.

Detection of in Vivo Enzyme Activity with CatalyCEST MRI Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. May, 2013 | Pubmed ID: 23640714 PURPOSE: CatalyCEST MRI compares the detection of an enzyme-responsive chemical exchange saturation transfer (CEST) agent with the detection of an unresponsive "control" CEST agent that accounts for other conditions that influence CEST. The purpose of this study was to investigate the feasibility of in vivo catalyCEST MRI. METHODS: CEST agents that were responsive and unresponsive to the activity of urokinase plasminogen activator were shown to have negligible interaction with each other. A CEST-fast imaging with steady state precession (FISP) MRI protocol was used to acquire MR CEST spectroscopic images with a Capan-2 pancreatic tumor model after intravenous injection of the CEST agents. A function of (super)-Lorentzian line shapes was fit to CEST spectra of a region-of-interest that represented the tumor. RESULTS: The CEST effects from each agent showed the same initial uptake into tumor tissues, indicating that both agents had the same pharmacokinetic transport rates. Starting 5 min after injection, CEST from the enzyme-responsive agent disappeared more quickly than CEST from the unresponsive agent, indicating that the enzyme responsive agent was being catalyzed by urokinase plasminogen activator, while both agents also experienced net pharmacokinetic washout from the tumor. CONCLUSION: CatalyCEST MRI demonstrates that dynamic tracking of enzyme-responsive and unresponsive CEST agents during the same in vivo MRI study is feasible. Magn Reson Med, 2013. Â© 2013 Wiley Periodicals, Inc.

Intestinal Caveolin-1 is Important for Dietary Fatty Acid Absorption Biochimica Et Biophysica Acta. May, 2013 | Pubmed ID: 23665238 How dietary fatty acids are absorbed into the enterocyte and transported to the ER is not established. We tested the possibility that caveolin-1 containing lipid rafts and endocytic vesicles were involved. Apical brush border membranes took up 15% of albumin bound (3)H-oleate whereas brush border membranes from caveolin-1 KO mice took up only 1%. In brush border membranes, the (3)H-oleate was in the detergent resistant fraction of an OptiPrep gradient. On OptiPrep gradients of intestinal cytosol, we also found the (3)H-oleate in the detergent resistant fraction, separate from OptiPrep gradients spiked with (3)H-oleate or (3)H-triacylglycerol. Caveolin-1 immuno-depletion of cytosol removed 91% of absorbed (3)H-oleate whereas immuno-depletion using IgG, or anti-caveolin-2 or -3 or anti-clathrin antibodies removed 20%. Electron microscopy showed the presence of caveolin-1 containing vesicles in WT mouse cytosol that were 4 fold increased by feeding intestinal sacs 1mM oleate. No vesicles were seen in caveolin-1 KO mouse cytosol. Caveolin-1 KO mice gained less weight on a 23% fat diet and had increased fat in their stool compared to WT mice. We conclude that dietary fatty acids are absorbed by caveolae in enterocyte brush border membranes, are endocytosed, and transported in cytosol in caveolin-1 containing endocytic vesicles.

Intranasal Myiasis: a Rare Complication of Transnasal Skull Base Surgery Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. Aug, 2013 | Pubmed ID: 23669173 A 57-year-old woman with a history of atypical intracranial meningioma had undergone multiple craniotomies and endoscopic skull base procedures over several years. She presented most recently with nasal discharge consisting of intranasal larvae. Isolated organisms from the nasal cavity and maxillary sinus were identified as blow fly larvae (Calliphoridae family). The patient was treated with transnasal debridement and antibiotic therapy. The organisms were successfully eradicated and she is free from further signs of infection. Intranasal myiasis is an unusual complication of anterior skull base surgery.

Essential Role of NADPH Oxidase-Dependent Reactive Oxygen Species Generation in Regulating MicroRNA-21 Expression and Function in Prostate Cancer Antioxidants & Redox Signaling. Jul, 2013 | Pubmed ID: 23682737 Abstract Aims: Oncogenic microRNAs (miRs) promote tumor growth and invasiveness. One of these, miR-21, contributes to carcinogenesis in prostate and other cancers. In the present study, we tested the hypothesis that NADPH oxidase-dependent reactive oxygen species (ROS) regulate the expression and function of miR-21 and its target proteins, maspin and programmed cell death 4 (PDCD4), in prostate cancer cells. Results: The highly aggressive androgen receptor negative PC-3M-MM2 prostate cancer cells demonstrated high expression of miR-21 and p47(phox) (an essential subunit of NADPH oxidase). Using loss-of-function strategy, we showed that transfection of PC-3M-MM2 cells with anti-miR-21- and p47(phox) siRNA (si-p47(phox)) led to reduced expression of miR-21 with concurrent increase in maspin and PDCD4, and decreased the invasiveness of the cells. Tail-vein injections of anti-miR-21- and si-p47(phox)-transfected PC-3M-MM2 cells in severe combined immunodeficient mice reduced lung metastases. Clinical samples from patients with advanced prostate cancer expressed high levels of miR-21 and p47(phox), and low expression of maspin and PDCD4. Finally, ROS activated Akt in these cells, the inhibition of which reduced miR-21 expression. Innovation: The levels of NADPH oxidase-derived ROS are high in prostate cancer cells, which have been shown to be involved in their growth and migration. This study demonstrates that ROS produced by this pathway is essential for the expression and function of an onco-miR, miR-21, in androgen receptor-negative prostate cancer cells. Conclusion: These data demonstrate that miR-21 is an important target of ROS, which contributes to the highly invasive and metastatic phenotype of prostate cancer cells. Antioxid. Redox Signal. 00, 000-000.

Clinical Features of Brain Metastasis from Salivary Gland Tumors Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. May, 2013 | Pubmed ID: 23685104 Salivary gland tumors comprise a group of 24 tumor subtypes with a wide range of clinical behaviors and propensities for metastasis. Several prognostic factors have been identified that help predict the development of systemic metastases, most commonly to the lung, liver, or bone. Metastases to the brain are rare. To better understand the behavior of salivary gland tumors that metastasise to the brain, we performed a retrospective cohort analysis on a series of patients to highlight features of their medical and surgical management. From 2007 to 2011, a database of 4117 elective craniotomies were queried at a single institution to identify patients surgically treated for salivary gland metastases to the brain. Three patients were identified. Histologic subtypes included salivary duct carcinoma, poorly differentiated carcinoma, and papillary mucinous adenocarcinoma. They had all undergone previous treatment for their primary malignancy. The mean time to intracranial metastasis was 48months from initial diagnosis (range, 14-91months). Treatment for intracranial metastases included surgical resection, whole brain radiation, stereotactic radiosurgery, and chemotherapy. Intracranial metastases from salivary gland tumors are rare, present years after diagnosis of the primary tumor, and are treatable with multimodality therapy.

Non-contrast 3D Time-of-flight Magnetic Resonance Angiography for Visualization of Intracranial Aneurysms in Patients with Absolute Contraindications to CT or MRI Contrast Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. Aug, 2013 | Pubmed ID: 23685107 The preoperative evaluation of patients with intracranial aneurysms typically includes a contrast-enhanced vascular study, such as computed tomography angiography (CTA), magnetic resonance angiography (MRA), or digital subtraction angiography. However, there are numerous absolute and relative contraindications to the administration of imaging contrast agents, including pregnancy, severe contrast allergy, and renal insufficiency. Evaluation of patients with contrast contraindications thus presents a unique challenge. We identified three patients with absolute contrast contraindications who presented with intracranial aneurysms. One patient was pregnant, while the other two had previous severe anaphylactic reactions to iodinated contrast. Because of these contraindications to intravenous contrast, we performed non-contrast time-of-flight MRA with 3D reconstruction (TOF MRA with 3DR) with maximum intensity projections and volume renderings as part of the preoperative evaluation prior to successful open surgical clipping of the aneurysms. In the case of one paraclinoid aneurysm, a high-resolution non-contrast CT scan was also performed to assess the relationship of the aneurysm to the anterior clinoid process. TOF MRA with 3DR successfully identified the intracranial aneurysms and adequately depicted the surrounding microanatomy. Intraoperative findings were as predicted by the preoperative imaging studies. The aneurysms were successfully clip-obliterated, and the patients had uneventful post-operative courses. These cases demonstrate that non-contrast imaging is a viable modality to assess intracranial aneurysms as part of the surgical planning process in patients with contrast contraindications. TOF MRA with 3DR, in conjunction with high-resolution non-contrast CT when indicated, provides adequate visualization of the microanatomy of the aneurysm and surrounding structures.

Novel Approaches to the Primary Prevention of Edema After Ischemia Stroke; a Journal of Cerebral Circulation. Jun, 2013 | Pubmed ID: 23709712

Regulatory B-cell Compartment in Transfused Alloimmunized and Non-alloimmunized Patients with Sickle Cell Disease American Journal of Hematology. Sep, 2013 | Pubmed ID: 23720018 Transfusion therapy is a life-sustaining treatment for patients with sickle cell disease (SCD), but can cause serious complications including alloimmunization. We previously reported diminished regulatory T cells (Tregs) and skewed Th2 responses in alloimmunized SCD patients. We hypothesized that the B cell regulatory (Breg) compartment, which controls Treg and Th differentiation, may also be compromised in allosensitized SCD patients. Phenotypically, we did not find differences in the frequency or numbers of CD24(hi) CD38(hi) and CD24(hi) CD27(+) B cell subsets, both previously identified as human Bregs, between alloimmunized and non-alloimmunized SCD patients on regular transfusions. However, at the functional level, CD19+ B cells from alloimmunized SCD patients expressed lower levels of IL-10 following stimulation as compared with non-alloimmunized patients (P < 0.05), and had reduced ability in inhibiting autologous CD14+ monocyte TNF-Î± expression (P < 0.05). These findings suggest that Bregs from alloimmunized and non-alloimmunized SCD patients differ in their ability to produce IL-10 and dampen monocyte activation, all consistent with an altered immunoregulatory state in alloimmunized SCD patients. Am. J. Hematol. 88:736-740, 2013. Â© 2013 Wiley Periodicals, Inc.

MR Characterization of Hepatic Storage Iron in Transfusional Iron Overload Journal of Magnetic Resonance Imaging : JMRI. May, 2013 | Pubmed ID: 23720394 PURPOSE: To quantify the two principal forms of hepatic storage iron, diffuse, soluble iron (primarily ferritin), and aggregated, insoluble iron (primarily hemosiderin) using a new MRI method in patients with transfusional iron overload. MATERIALS AND METHODS: Six healthy volunteers and 20 patients with transfusion-dependent thalassemia syndromes and iron overload were examined. Ferritin- and hemosiderin-like iron were determined based on the measurement of two distinct relaxation parameters: the "reduced" transverse relaxation rate, RR2 , and the "aggregation index," A, using three sets of Carr-Purcell-Meiboom-Gill (CPMG) datasets with different interecho spacings. Agarose phantoms, simulating the relaxation and susceptibility properties of tissue with different concentrations of dispersed (ferritin-like) and aggregated (hemosiderin-like) iron, were used for validation. RESULTS: Both phantom and in vivo human data confirmed that transverse relaxation components associated with the dispersed and aggregated iron could be separated using the two-parameter (RR2 , A) method. The MRI-determined total hepatic storage iron was highly correlated (râ€‰=â€‰0.95) with measurements derived from biopsy or biosusceptometry. As total hepatic storage iron increased, the proportion stored as aggregated iron became greater. CONCLUSION: This method provides a new means for noninvasive MRI determination of the partition of hepatic storage iron between ferritin and hemosiderin in iron overload disorders. J. Magn. Reson. Imaging 2013;. Â© 2013 Wiley Periodicals, Inc.

Diagnostic Potential of Iris Cross-sectional Imaging in Albinism Using Optical Coherence Tomography Ophthalmology. May, 2013 | Pubmed ID: 23725737 PURPOSE: To characterize inÂ vivo anatomic abnormalities of the iris in albinism compared with healthy controls using anterior segment optical coherence tomography (AS-OCT) and to explore the diagnostic potential of this technique for albinism. We also investigated the relationship between iris abnormalities and other phenotypical features of albinism. DESIGN: Prospective cross-sectional study. PARTICIPANTS: A total of 55 individuals with albinism and 45 healthy controls. METHODS: We acquired 4.37Ã—4.37-mm volumetric scans (743 A-scans, 50 B-scans) of the nasal and temporal iris in both eyes using AS-OCT (3-Î¼m axial resolution). Iris layers were segmented and thicknesses were measured using ImageJ software. Iris transillumination grading was graded using Summers and colleagues' classification. Retinal OCT, eye movement recordings, best-corrected visual acuity (BCVA), visual evoked potential (VEP), and grading of skin and hair pigmentation were used to quantify other phenotypical features associated with albinism. MAIN OUTCOME MEASURES: Iris AS-OCT measurements included (1) total iris thickness, (2) stroma/anterior border (SAB) layer thickness, and (3) posterior epithelial layer (PEL) thickness. Correlation with other phenotypical measurements, including (1) iris transillumination grading, (2) retinal layer measurements at the fovea, (3) nystagmus intensity, (4) BCVA, (5) VEP asymmetry, (6) skin pigmentation, and (7) hair pigmentation (of head hair, lashes, and brows). RESULTS: The mean iris thickness was 10.7% thicker in controls (379.3Â±44.0 Î¼m) compared with the albinism group (342.5Â±52.6 Î¼m; P>0.001), SAB layers were 5.8% thicker in controls (315.1Â±43.8 Î¼m) compared with the albinism group (297.7Â±50.0 Î¼m; P=0.044), and PEL was 44.0% thicker in controls (64.1Â±11.7 Î¼m) compared with the albinism group (44.5Â±13.9 Î¼m; P

Barriers to Drug Delivery in Interventional Oncology Journal of Vascular and Interventional Radiology : JVIR. Aug, 2013 | Pubmed ID: 23735316 Although much attention has been paid to mechanisms of anticancer drug resistance that focus on intracellular processes that protect tumor cells, it has recently become increasingly evident that the unique features of the tumor microenvironment profoundly impact the efficacy of cancer therapies. The properties of this extracellular milieu, including increased interstitial pressure, decreased pH, hypoxia, and abnormal vascularity, result in limited drug efficacy; this finding is true not only for systemic chemotherapy but also for catheter-based therapies, including chemoembolization and radioembolization. The present review summarizes the barriers to drug delivery imposed by the tumor microenvironment and provides methods to overcome these hurdles.

Self-nanoemulsifying Drug Delivery System of Glimepiride: Design, Development, and Optimization PDA Journal of Pharmaceutical Science and Technology / PDA. May, 2013 | Pubmed ID: 23752748 The objective of the present investigation was to develop and characterize the self-nanoemulsifying drug delivery system (SNEDDS) of glimepiride, a poorly soluble drug. Solubility of glimepiride in various vehicles was determined, and ternary phase diagrams were constructed using a suitable oil, surfactant, and cosurfactant system to find out the efficient self-emulsification system. A three factor, three level Box-Behnken statistical design was employed to explore the main and interaction effect of independent variables, namely X1 (amount of Capmul MCM), X2 (amount of Acrysol K 140), and X3 (amount of Transcutol P). Percent transmittance value (Y1), droplet diameter (Y2), and percent drug released at 5 min (Y3) were the dependent variables. Formulation optimization was carried out to optimize the droplet diameter and percent drug dissolved at 5 min. The batch prepared according to the optimized formulation showed a close agreement between observed and predicted values. Box-Behnken statistical design allowed us to understand the effect of formulation variables on the rapid dissolution of drug from SNEDDS and to optimize the formulation to obtain a rapid drug dissolution at 5 min.

Pars Plana Vitrectomy Versus Combined Pars Plana Vitrectomy-scleral Buckle for Secondary Repair of Retinal Detachment Ophthalmic Surgery, Lasers & Imaging Retina. Jul-Aug, 2013 | Pubmed ID: 23758323 To investigate the optimal technique for repairing recurrent rhegmatogenous retinal detachments.

Persistent Hyaloid Artery with an Aberrant Peripheral Retinal Attachment: A Unique Presentation Oman Journal of Ophthalmology. Jan, 2013 | Pubmed ID: 23772130

Sickle Cell Disease: Time for a Closer Look at Treatment Options? British Journal of Haematology. Aug, 2013 | Pubmed ID: 23772687 Tremendous progress has been made in the care of individuals with sickle cell over the past several decades. Major successes have been comprehensive infection prophylaxis, prediction and prevention of stroke, and better transfusion care, the latter including both prevention of alloimmunization and treatment of iron overload. However, definitive therapies remain limited to hydroxycarbamide (hydroxyurea) and stem cell transplantation, both of which have been in use for at least two decades. Despite knowing the progressive natural history of the disease with organ dysfunction, failure, and ultimately death at a young age, definitive therapies are considered for only a small proportion of individuals. Consequently, while life expectancy has improved dramatically from the last century, the ongoing pace of advancement has slowed or stalled. We believe that it is time to broaden the use of definitive therapy for those with asymptomatic disease, being cautiously more aggressive in our approach.

Image of the Month. Perforated Small-bowel Diverticulum with Calcified Fecalith JAMA Surgery. Jun, 2013 | Pubmed ID: 23783257

Sleep's Role in Human Spatial Learning Sleep. 2013 | Pubmed ID: 23814331

Chromosomal Imbalance Letter: Phenotypic Consequences of Combined Deletion 8pter and Duplication 15qter Molecular Cytogenetics. Jul, 2013 | Pubmed ID: 23815819 Exact breakpoint determination by oligonucleotide array-CGH has improved the analysis of genotype-phenotype correlations in cases with chromosome aberrations allowing a more accurate definition of relevant genes, particularly their isolated or combined impact on the phenotype in an unbalanced state. Chromosomal imbalances have been identified as one of the major causes of mental retardation and/or malformation syndromes and they are observed in ~2-5 % of the cases. Here we report a female child born to non-consanguineous parents and having multiple congenital anomalies such as atrial septal defect and multiple ventricular septal defects, convergent strabismus, micropthalmia, seizures and mental retardation, with her head circumference and stature normal for her age. Cytogenetic study suggested 46,XX,add(8)(p23). Further analysis by array-CGH using 44 K oligonucleotide probe confirmed deletion on 8p23.3p23.1 of 7.1 Mb and duplication involving 15q23q26.3 of 30 Mb size leading to 46XX,der(8)t(8;15)(p23.3;q23)pat.arr 8p23.3p23.1(191,530-7,303,237)x1,15q23q26.3(72,338,961-102,351,195)x3. The unique phenotypic presentation in our case may have resulted from either loss or gain of a series of contiguous genes which may have resulted in a direct phenotypic effect and/or caused a genetic regulatory disturbance. Double segmental aberrations may have conferred phenotypic variability, as in our case, making it difficult to predict the characteristics that evolved as a result of the global gene imbalance, caused by the concomitant deletion and duplication.

Multiple Axillary Papules in an Infant. Diagnosis: Multiple Congenital Apocrine Hidrocystomas Pediatric Dermatology. Jul-Aug, 2013 | Pubmed ID: 23819451

Novel Conserved Genotypes Correspond to Antibiotic Resistance Phenotypes of E. Coli Clinical Isolates PloS One. 2013 | Pubmed ID: 23824211 Current efforts to understand antibiotic resistance on the whole genome scale tend to focus on known genes even as high throughput sequencing strategies uncover novel mechanisms. To identify genomic variations associated with antibiotic resistance, we employed a modified genome-wide association study; we sequenced genomic DNA from pools of E. coli clinical isolates with similar antibiotic resistance phenotypes using SOLiD technology to uncover single nucleotide polymorphisms (SNPs) unanimously conserved in each pool. The multidrug-resistant pools were genotypically similar to SMS-3-5, a previously sequenced multidrug-resistant isolate from a polluted environment. The similarity was evenly spread across the entire genome and not limited to plasmid or pathogenicity island loci. Among the pools of clinical isolates, genomic variation was concentrated adjacent to previously reported inversion and duplication differences between the SMS-3-5 isolate and the drug-susceptible laboratory strain, DH10B. SNPs that result in non-synonymous changes in gyrA (encoding the well-known S83L allele associated with fluoroquinolone resistance), mutM, ligB, and recG were unanimously conserved in every fluoroquinolone-resistant pool. Alleles of the latter three genes are tightly linked among most sequenced E. coli genomes, and had not been implicated in antibiotic resistance previously. The changes in these genes map to amino acid positions in alpha helices that are involved in DNA binding. Plasmid-encoded complementation of null strains with either allelic variant of mutM or ligB resulted in variable responses to ultraviolet light or hydrogen peroxide treatment as markers of induced DNA damage, indicating their importance in DNA metabolism and revealing a potential mechanism for fluoroquinolone resistance. Our approach uncovered evidence that additional DNA binding enzymes may contribute to fluoroquinolone resistance and further implicate environmental bacteria as a reservoir for antibiotic resistance.

A Randomized, Phase 2, Dose-ranging Study in the Treatment of Moderate to Severe Inflammatory Facial Acne Vulgaris with Doxycycline Calcium Journal of Drugs in Dermatology : JDD. Jun, 2013 | Pubmed ID: 23839182 Doxycycline calcium (WC2055) is a drug substance with a possible role in the treatment of acne. The objective of this study was to evaluate the safety and efficacy of three doses of doxycycline calcium tablets compared with placebo in the treatment of moderate to severe inflammatory facial acne vulgaris.

Outcomes in Severe Middle Cerebral Artery Ischemic Stroke Neurocritical Care. Jul, 2013 | Pubmed ID: 23839704 Severe middle cerebral artery stroke (MCA) is associated with a high rate of morbidity and mortality. We assessed the hypothesis that patient-specific variables may be associated with outcomes. We also sought to describe under-recognized patient-centered outcomes.

Epidemic Dropsy: Epidemiological, Clinical & Therapeutic Observations in 67 Cases. 1969 The Indian Journal of Medical Research. Apr, 2013 | Pubmed ID: 23841192

Burden of Lysosomal Storage Disorders in India: Experience of 387 Affected Children from a Single Diagnostic Facility JIMD Reports. Jul, 2013 | Pubmed ID: 23852624 Lysosomal storage disorders (LSDs) are considered to be a rare metabolic disease for the national health forum, clinicians, and scientists. This study aimed to know the prevalence of different LSDs, their geographical variation, and burden on the society. It included 1,110 children from January 2002 to December 2012, having coarse facial features, hepatomegaly or hepatosplenomegaly, skeletal dysplasia, neuroregression, leukodystrophy, developmental delay, cerebral-cerebellar atrophy, and abnormal ophthalmic findings. All subjects were screened for I-cell disease, glycolipid storage disorders (Niemann-Pick disease A/B, Gaucher), and mucopolysaccharide disorders followed by confirmatory lysosomal enzymes study from leucocytes and/or fibroblasts. Niemann-Pick disease-C (NPC) was confirmed by fibroblasts study using filipin stain. Various storage disorders were detected in 387 children (34.8 %) with highest prevalence of glycolipid storage disorders in 48 %, followed by mucopolysaccharide disorders in 22 % and defective sulfatide degradation in 14 % of the children. Less common defects were glycogen degradation defect and protein degradation defect in 5 % each, lysosomal trafficking protein defect in 4 %, and transport defect in 3 % of the patients. This study demonstrates higher incidence of Gaucher disease (16 %) followed by GM2 gangliosidosis that includes Tay-Sachs disease (10 %) and Sandhoff disease (7.8 %) and mucopolysaccharide disorders among all LSDs. Nearly 30 % of the affected children were born to consanguineous parents and this was higher (72 %) in children with Batten disease. Our study also demonstrates two common mutations c.1277_1278insTATC in 14.28 % (4/28) and c.964G>T (p.D322Y) in 10.7 % (3/28) for Tay-Sachs disease in addition to the earlier reported c.1385A>T (p.E462V) mutation in 21.42 % (6/28).

Factors That Predict 1-Month Mortality in Patients With Pregnancy-Specific Liver Disease Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association. Jul, 2013 | Pubmed ID: 23856360 Pregnancy-specific liver diseases such as acute fatty liver of pregnancy; hemolysis, elevated liver enzymes and low platelet syndrome; and preeclampsia-associated liver disease are associated with considerable morbidity and mortality. We investigated the ability of the model for end-stage liver disease (MELD) to predict 1-month mortality among patients with pregnancy-specific liver diseases. We also developed and tested a model to predict mortality based on features of pregnancy-specific liver diseases.

Association of Complications with Blood Transfusions in Pediatric Cardiac Surgery Patients The Annals of Thoracic Surgery. Sep, 2013 | Pubmed ID: 23866807 Blood product transfusion during cardiopulmonary bypass has been demonstrated to be associated with increased morbidity and mortality in adult cardiac surgery populations. The aim of this study was to characterize the risk-adjusted occurrence of postoperative complications and mortality in relation to intraoperative blood product transfusion in our pediatric cardiac surgery population.

Potential Communicative Acts in Children with Autism Spectrum Disorders Developmental Neurorehabilitation. Jul, 2013 | Pubmed ID: 23869845 Abstract Objective: To describe potential communicative acts in a sample of 17 children with autism spectrum disorders who produced few to no intelligible words (mean ageâ€‰=â€‰32.82 months). Methods: Parents reported on children's potential communicative acts for 10 different communicative functions. A potential communicative act was defined as any behavior produced by an individual that may be interpreted by others to serve a communicative purpose. Results: Significant associations were found between higher number of gesture types and increased scores on language comprehension, language expression, and non-verbal thinking measures. Relative to other types of potential communicative acts, parents reported that children used higher proportions of body movement. Conclusion: Number of body movement types was not related to child ability, while number of gesture types was related to receptive and expressive language. Findings underscore the link between language and gesture, and offer support for an ecological systems perspective of language learning.

PREDOSE: A Semantic Web Platform for Drug Abuse Epidemiology Using Social Media Journal of Biomedical Informatics. Jul, 2013 | Pubmed ID: 23892295 The role of social media in biomedical knowledge mining, including clinical, medical and healthcare informatics, prescription drug abuse epidemiology and drug pharmacology, has become increasingly significant in recent years. Social media offers opportunities for people to share opinions and experiences freely in online communities, which may contribute information beyond the knowledge of domain professionals. This paper describes the development of a novel semantic web platform called PREDOSE (PREscription Drug abuse Online Surveillance and Epidemiology), which is designed to facilitate the epidemiologic study of prescription (and related) drug abuse practices using social media. PREDOSE uses web forum posts and domain knowledge, modeled in a manually created Drug Abuse Ontology (DAO - pronounced dow), to facilitate the extraction of semantic information from User Generated Content (UGC), through combination of lexical, pattern-based and semantics-based techniques. In a previous study, PREDOSE was used to obtain the datasets from which new knowledge in drug abuse research was derived. Here, we report on various platform enhancements, including an updated DAO, new components for relationship and triple extraction, and tools for content analysis, trend detection and emerging patterns exploration, which enhance the capabilities of the PREDOSE platform. Given these enhancements, PREDOSE is now more equipped to impact drug abuse research by alleviating traditional labor-intensive content analysis tasks.

Angiographic Features Help Predict Outcome After Stereotactic Radiosurgery for the Treatment of Pediatric Arteriovenous Malformations Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery. Jul, 2013 | Pubmed ID: 23892391 Arteriovenous malformations (AVMs) are a frequent cause of hemorrhagic stroke in children. Stereotactic radiosurgery (SRS) is an established treatment for these lesions, particularly those that are surgically inaccessible. Because only complete AVM obliteration is believed to protect against the future risk of hemorrhage, identifying lesion characteristics that predict response to therapy is an important objective. The goal of this study is to evaluate the influence of angiographic features of AVMs on the rate of obliteration following treatment with SRS.

Laparoscopic Reduction of Ileoileal Intussusception in Henoch-Schonlein Purpura BMJ Case Reports. 2013 | Pubmed ID: 23904434

The Influence of Initial Atomized Droplet Size on Residual Particle Size from Pressurized Metered Dose Inhalers International Journal of Pharmaceutics. Oct, 2013 | Pubmed ID: 23911912 Pressurized metered dose inhalers (pMDIs) are widely used for the treatment of diseases of the lung, including asthma and chronic obstructive pulmonary disease. The mass median aerodynamic diameter of the residual particles (MMADR) delivered from a pMDI plays a key role in determining the amount and location of drug deposition in the lung and thereby the efficacy of the inhaler. The mass median diameter of the initial droplets (MMDI), upon atomization of a formulation, is a significant factor influencing the final particle size. The purpose of this study was to evaluate the extent that MMDI and initial droplet geometric standard deviation (GSD) influence the residual aerodynamic particle size distribution (APSDR) of solution and suspension formulations. From 48 solution pMDI configurations with varying ethanol concentrations, valve sizes and actuator orifice diameters, it was experimentally found that the effective MMDI ranged from 7.8 to 13.3Î¼m. Subsequently, computational methods were utilized to determine the influence of MMDI on MMADR, by modulating the MMDI for solution and suspension pMDIs. For solution HFA-134a formulations of 0.5% drug in 10% ethanol, varying the MMDI from 7.5 to 13.5Î¼m increased the MMADR from 1.4 to 2.5Î¼m. For a suspension formulation with a representative particle size distribution of micronized drug (MMAD=2.5Î¼m, GSD=1.8), the same increase in MMDI resulted in an increase in the MMADR from 2.7 to only 3.3Î¼m. Hence, the same increase in MMDI resulted in a 79% increase in MMADR for the solution formulation compared to only a 22% increase for the suspension formulation. Similar trends were obtained for a range of drug concentrations and input micronized drug sizes. Thus, APSDR is more sensitive to changes in MMDI for solution formulations than suspension formulations; however, there are situations in which hypothetically small micronized drug in suspension (e.g. 500nm MMAD) could resemble trends observed for solution formulations. Furthermore, the relationship between APSDR and drug concentration and MMDI is predictable for solution pMDIs, but this is not as straightforward for suspension formulations. In addition, the MMADR was relatively insensitive to changes in initial droplet GSD (from 1.6 to 2.0) and the solution and suspension pMDI residual particle GSDs were essentially identical to the initial droplet GSDs.

"Self-regulation," a New Facet of Hox Genes' Function Developmental Dynamics : an Official Publication of the American Association of Anatomists. Jul, 2013 | Pubmed ID: 23913823 Background: Precise temporal and spatial expression of the clustered Hox genes is essential for patterning the developing embryo. Temporal activation of Hox genes was shown to be cluster-autonomous. However, gene clustering appears dispensable for spatial colinear expression. Generally, a set of Hox genes expressed in a group of cells instructs these cells about their fate such that the differential expression of Hox genes results in morphological diversity. The spatial colinearity is considered to rely both on local and long-range cis regulation. Results: Here, we report on the global deregulation of HoxA and HoxD expression patterns upon inactivation of a subset of HOXA and HOXD proteins. Conclusions: Our data suggest the existence of a "self-regulation" mechanism, a process by which HOX proteins establish and/or maintain the spatial domains of the Hox gene family and we propose that the functionally dominant HOX proteins could contribute to generating the spatial parameters of Hox expression in a given tissue, i.e., HOX controlling the establishment of the ultimate HOX code. Developmental Dynamics, 2013. Â© 2013 Wiley Periodicals, Inc.

Prediction of Poor Outcome in Cerebellar Infarction by Diffusion MRI Neurocritical Care. Aug, 2013 | Pubmed ID: 23921570 Identification of patients with posterior fossa infarction at risk for neurological deterioration remains a challenge. MRI-based assessments of MCA infarction can predict poor outcome. Similar quantitative imaging measures after cerebellar stroke have not been studied. We tested the hypothesis that MRI-based volumetric assessment of cerebellar infarcts can provide reliable information for the prediction of poor outcome.

A Pilot Study of Surgical Training Using a Virtual Robotic Surgery Simulator JSLS : Journal of the Society of Laparoendoscopic Surgeons / Society of Laparoendoscopic Surgeons. Apr-Jun, 2013 | Pubmed ID: 23925015 Our objectives were to compare the utility of learning a suturing task on the virtual reality da Vinci Skills Simulator versus the da Vinci Surgical System dry laboratory platform and to assess user satisfaction among novice robotic surgeons.

Seizures from Valproate-carbapenem Interaction Pediatric Neurology. Oct, 2013 | Pubmed ID: 23932807 Antiepileptic medication interactions can complicate the management of epilepsy, by either increasing or reducing the effective serum concentrations thereby causing adverse effects or loss of seizure control.

Mystery Case: An Unexpected Complication of IV Thrombolysis for Acute Ischemic Stroke Neurology. Aug, 2013 | Pubmed ID: 23940024 A 46-year-old man with psoriasis and morbid obesity developed acute aphasia and right hemiplegia. As a result of his weakness, he had fallen and struck his right eye on a desk. His presenting examination demonstrated right periorbital ecchymosis without accompanying ptosis, expressive aphasia, left gaze deviation with corresponding hemianopsia, and dense right hemiplegia, summating an NIH Stroke Scale score of 13.

Microsurgical Rat Varicocele Model The Journal of Urology. Aug, 2013 | Pubmed ID: 23954374 A rat varicocele model using partial occlusion of the left renal vein has previously been described; reproducibility in creation of this model has met with varied success. Alternate routes of testicular venous drainage may negate the effect of partial renal vein occlusion on varicocele creation. We hypothesized that varicocele induction would be more effective if microsurgical ligation of the gonadal venous drainage to the common iliac vein was combined with partial occlusion of the left renal vein.

Road Traffic Injury Mortality and Its Mechanisms in India: Nationally Representative Mortality Survey of 1.1 Million Homes BMJ Open. 2013 | Pubmed ID: 23959748 To quantify and describe the mechanism of road traffic injury (RTI) deaths in India.

Interaction of Finger Representations in the Cortex of Individuals with Autism: A Functional Window into Cortical Inhibition Autism Research : Official Journal of the International Society for Autism Research. Aug, 2013 | Pubmed ID: 23983203 An established neural biomarker of autism spectrum disorder (ASD) has the potential to provide novel biological and pharmacological targets for treatment. Lower level of inhibition in brain circuits is a leading biomarker candidate. A physiological investigation of the functional levels of inhibition in the cortex of individuals with autism can provide a strong test of the hypothesis. The amplitude of cortical response to the stimulation of adjacent fingers is controlled by the level of cortical inhibition and provides just such a test. Using magnetoencephalography, we recorded the response of the somatosensory cortex to the passive tactile stimulation of the thumb (D1), and index finger (D2), and to the simultaneous stimulation of both fingers combined (D1,D2) of the dominant (right) hand of young subjects with and without autism. For each participant, we measured the response to the stimulation of both fingers combined (D1,D2) relative to the post hoc sum of the responses to the stimulation of each finger alone (D1+D2) in multiple different ways and linearly regressed the ASD and neurotypical (NT) groups' responses. The resulting slopes were then compared: Smaller slope values imply attenuated response to paired finger stimulation, and enhanced levels of inhibition. The short-latency M40 and mid-latency M80 response slopes of the group with autism obtained in different ways were either significantly smaller, or statistically indistinguishable from NT. The result does not support reduced inhibition in the somatosensory cortex of individuals with autism, contrary to the seminal hypothesis of reduced inhibition. Implications are discussed including refinements of current theory. Autism Res 2013, â—â—: â—â—-â—â—. Â© 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Low-Sodium DASH Diet Improves Diastolic Function and Ventricular-Arterial Coupling in Hypertensive Heart Failure with Preserved Ejection Fraction Circulation. Heart Failure. Aug, 2013 | Pubmed ID: 23985432 -Heart failure with preserved ejection fraction (HFPEF) involves failure of cardiovascular reserve in multiple domains. In HFPEF animal models, dietary sodium restriction improves ventricular and vascular stiffness and function. We hypothesized that the sodium-restricted Dietary Approaches to Stop Hypertension diet (DASH/SRD) would improve left ventricular diastolic function, arterial elastance, and ventricular-arterial (V-A) coupling in hypertensive HFPEF.

The Incidence of Complications in Elective Cranial Neurosurgery Associated with Dural Closure Material Journal of Neurosurgery. Sep, 2013 | Pubmed ID: 24032702 Object Dural closure with synthetic grafts has been suggested to contribute to the incidence of infection and CSF leak. The objective of this study was to assess the contribution of choice of dural closure material, as well as other factors, to the incidence of infection and CSF leak. Methods A retrospective, consecutive cohort study of adult patients undergoing elective craniotomy was established between April 2010 and March 2011 at a single center. Exclusion criteria consisted of trauma, bur hole placement alone, and temporary CSF fluid diversion. Results Three hundred ninety-nine patients were included (mean follow-up 396.6 days). Nonautologous (synthetic) dural substitute was more likely to be used (n = 106) in cases of reoperation (p = 0.001). Seventeen patients developed a surgical site infection and 12 patients developed a CSF leak. Multivariate logistic regression modeling identified estimated blood loss (OR 1.002, 95% CI 1.001-1.003; p < 0.001) and cigarette smoking (OR 2.198, 95% CI 1.109-4.238; p = 0.019) as significant predictors of infection. Synthetic dural graft was not a predictor of infection in multivariate analysis. Infratentorial surgery (OR 4.348, 95% CI 1.234-16.722; p = 0.024) and more than 8 days of postoperative corticosteroid treatment (OR 3.886, 95% CI 1.052-16.607; p = 0.048) were significant predictors for the development of CSF leak. Synthetic dural graft was associated with a lower likelihood of CSF leak (OR 0.072, 95% CI 0.003-0.552; p = 0.036). Conclusions The use of synthetic dural closure material is not associated with surgical site infection and is associated with a reduced incidence of CSF leak. Modifiable risk factors exist for craniotomy complications that warrant vigilance and further study.

Factors That Predict Mortality in Children with Wilson Disease Associated Acute Liver Failure and Comparison of Wilson Disease Specific Prognostic Indices Journal of Gastroenterology and Hepatology. Aug, 2013 | Pubmed ID: 24033813 Wilson disease (WD) associated acute liver failure (ALF) affects children more than adults. The predictors of mortality and outcome in patients without encephalopathy are not clear. We investigated the ability of prognostic factors and various models including model for end-stage liver disease to predict mortality among children with WD and ALF.

Canadian Cardiovascular Society Position Statement on Radiation Exposure From Cardiac Imaging and Interventional Procedures The Canadian Journal of Cardiology. Sep, 2013 | Pubmed ID: 24035289 Exposure to ionizing radiation is a consequence of many diagnostic and interventional cardiac procedures. Radiation exposure can result in detrimental health effects because of deterministic (eg, skin reaction) and stochastic effects (eg, cancer). However, with the levels experienced during cardiac procedures these risks can be difficult to quantify. Healthcare providers and patients might not fully appreciate radiation-related risks. Though in many cases radiation exposure cannot be avoided, a practice of minimizing exposures to levels "as low as reasonably achievable" (ALARA principle) without compromising the utility of the procedure is encouraged. The purpose of this document is to inform health care providers on the key concepts related to radiation risk from common cardiac procedures and provide specific recommendations on ensuring quality of care.

An Intraoperative Cholangiogram: Unusual Anatomy BMJ (Clinical Research Ed.). 2013 | Pubmed ID: 24037791

Autoimmune Pancreatitis The Gastroenterology Report. Apr, 2013 | Pubmed ID: 24040625 Autoimmune pancreatitis (AIP) is a rare, heterogeneous, fibroinflammatory disorder of the pancreas. It has gained increasing recognition due to a presentation that can mimic difficult to treat disorders such as pancreatic cancer, cholangiocarcinoma and primary sclerosing cholangitis. In contrast, autoimmune pancreatitis is a benign disease that is very responsive to therapy with corticosteroids. There are two types of AIP. Type 1 disease is the most common worldwide and is associated with extrapancreatic manifestations and elevated levels of IgG4-positive cells. Type 2 AIP is characterized by a paucity of IgG4-positive cells, and is more difficult to diagnose. This review provides an update on the diagnosis, pathophysiology and treatment of AIP, with special emphasis on the two subtypes.

Use of Brain Electrical Activity for the Identification of Hematomas in Mild Traumatic Brain Injury Journal of Neurotrauma. Sep, 2013 | Pubmed ID: 24040943 Abstract This study investigates the potential clinical utility in the emergency department (ED) of an index of brain electrical activity to identify intracranial hematomas. The relationship between this index and depth, size, and type of hematoma was explored. Ten minutes of brain electrical activity was recorded from a limited montage in 38 adult patients with traumatic hematomas (CT scan positive) and 38 mild head injured controls (CT negative) in the ED. The volume of blood and distance from recording electrodes were measured by blinded independent experts. Brain electrical activity data was submitted to a classification algorithm independently developed TBI-Index to identify the probability of a CT+ traumatic event. There was no significant relationship between the TBI-index and type of hematoma, or distance of the bleed from recording sites. A significant correlation was found between TBI-Index and blood volume. Sensitivity to hematomas was 100%, positive predictive value (PPV) was 74.5%, and positive likelihood ratio (PLR) was 2.92. The TBI-index, derived from brain electrical activity, demonstrates high accuracy for identification of traumatic hematomas. Further, this was not influenced by distance of the bleed from the recording electrodes, blood volume, or type of hematoma. Distance and volume limitations noted with other methods, (such as that based on near-infrared spectroscopy, NIS), were not found, thus suggesting the TBI-Index to be a potentially important adjunct to acute assessment of head injury. Due to the life threatening risk of undetected hematomas (false negatives), specificity was permitted to be lower, 66%, in exchange for extremely high sensitivity.

Duodenal Gastrointestinal Stromal Tumor Presenting As Massive Gastrointestinal Bleed Indian Journal of Gastroenterology : Official Journal of the Indian Society of Gastroenterology. Sep, 2013 | Pubmed ID: 24043400

Transposition of Great Arteries With Aortopulmonary Window: Our Surgical Experience The Annals of Thoracic Surgery. Sep, 2013 | Pubmed ID: 24045073 Transposition of the great arteries with aortopulmonary window is a rare congenital cardiac anomaly. An arterial switch operation with repair of the aortopulmonary window is the preferred operation in this subset. As the tissue between the great arteries is missing, it is considered to be a complex operation. The purpose of this study is to present our experience of a simple yet highly effective surgical technique for the management of this rare complex cardiac defect.

A Strategy for the Generation, Characterization and Distribution of Animal Models by The Michael J. Fox Foundation for Parkinson's Research Disease Models & Mechanisms. Sep, 2013 | Pubmed ID: 24046356 Progress in Parkinson's disease (PD) research and therapeutic development is hindered by many challenges, including a need for robust preclinical animal models. Limited availability of these tools is due to technical hurdles, patent issues, licensing restrictions and the high costs associated with generating and distributing these animal models. Furthermore, the lack of standardization of phenotypic characterization and use of varying methodologies has made it difficult to compare outcome measures across laboratories. In response, The Michael J. Fox Foundation for Parkinson's Research (MJFF) is directly sponsoring the generation, characterization and distribution of preclinical rodent models, enabling increased access to these crucial tools in order to accelerate PD research. To date, MJFF has initiated and funded the generation of 30 different models, which include transgenic or knockout models of PD-relevant genes such as Park1 (also known as Park4 and SNCA), Park8 (LRRK2), Park7 (DJ-1), Park6 (PINK1), Park2 (Parkin), VPS35, EiF4G1 and GBA. The phenotypic characterization of these animals is performed in a uniform and streamlined manner at independent contract research organizations. Finally, MJFF created a central repository at The Jackson Laboratory (JAX) that houses both non-MJFF and MJFF-generated preclinical animal models. Funding from MJFF, which subsidizes the costs involved in transfer, rederivation and colony expansion, has directly resulted in over 2500 rodents being distributed to the PD community for research use.

Microsurgical Denervation of Rat Spermatic Cord: Safety and Efficacy Data BJU International. Aug, 2013 | Pubmed ID: 24053156 To describe a microsurgical technique for denervation of the spermatic cord and use a multiphoton (MPM) laser to identify and ablate residual nerves after microsurgical denervation To evaluate structural and functional changes in the rat testis and vas deferens following denervation.

Semantics Driven Approach for Knowledge Acquisition from EMRs IEEE Journal of Biomedical and Health Informatics. Sep, 2013 | Pubmed ID: 24058038 Semantic computing technologies have matured to be applicable to many critical domains such as national security, life sciences, and health care. However, the key to their success is the availability of a rich domain knowledge base. The creation and refinement of domain knowledge bases poses difficult challenges. The existing knowledge bases in the health care domain are rich in taxonomic relationships, but they lack non-taxonomic (domain) relationships. In this paper, we describe a semi-automatic technique for enriching existing domain knowledge bases with causal relationships gleaned from Electronic Medical Records (EMR) data. We determine missing causal relationships between domain concepts by validating domain knowledge against EMR data sources and leveraging semantic-based techniques to derive plausible relationships that can rectify knowledge gaps. Our evaluation demonstrates that semantic techniques can be employed to improve the efficiency of knowledge acquisition.

Response Journal of Neurosurgery. Aug, 2013 | Pubmed ID: 24063045

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Articles by Heeral J. Sheth

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Articles by Heeral J. Sheth in JoVE

Bioengineering

Other articles by Heeral J. Sheth on PubMed

In JoVE (1)

Other Publications (200)

Articles by Heeral J. Sheth in JoVE

Bioengineering

Other articles by Heeral J. Sheth on PubMed

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