Cognitive-behavioral Therapy for Subthreshold Bulimia Nervosa: A Case Series

Eating and Weight Disorders : EWD. Sep, 2011  |  Pubmed ID: 22290037

The extent to which cognitive-behavioral therapy (CBT) is helpful in treating individuals with bulimic symptoms who do not meet full criteria for bulimia nervosa is unclear. The purpose of this investigation was to examine the potential efficacy of CBT for eating disorder individuals with bulimic symptoms who do not meet full criteria for bulimia nervosa. Twelve participants with subthreshold bulimia nervosa were treated in a case series with 20 sessions of CBT. Ten of the 12 participants (83.3%) completed treatment. Intent-to-treat abstinent percentages were 75.0% for objectively large episodes of binge eating (OBEs), 33.3% for subjectively large episodes of binge eating (SBEs), and 50% for purging at end of treatment. At one year follow-up, 66.7% were abstinent for OBEs, 41.7% for SBEs, and 50.0% for purging. The majority also reported improvements in associated symptoms. This case series provides support for the use of CBT with individuals with subthreshold bulimia nervosa.

Assessing the Benefits and Risks of Translocations in Changing Environments: a Genetic Perspective

Evolutionary Applications. Nov, 2011  |  Pubmed ID: 22287981

Translocations are being increasingly proposed as a way of conserving biodiversity, particularly in the management of threatened and keystone species, with the aims of maintaining biodiversity and ecosystem function under the combined pressures of habitat fragmentation and climate change. Evolutionary genetic considerations should be an important part of translocation strategies, but there is often confusion about concepts and goals. Here, we provide a classification of translocations based on specific genetic goals for both threatened species and ecological restoration, separating targets based on 'genetic rescue' of current population fitness from those focused on maintaining adaptive potential. We then provide a framework for assessing the genetic benefits and risks associated with translocations and provide guidelines for managers focused on conserving biodiversity and evolutionary processes. Case studies are developed to illustrate the framework.

Classification-based Approach for Management of an Adolescent with LBP, Lower Extremity Pain, and a Relevant Postural Deformity

The Journal of Manual & Manipulative Therapy. Feb, 2011  |  Pubmed ID: 22294853

A 15-year-old female presented to physical therapy 2 months after a traumatic injury with severe low back pain, referred unilateral leg pain below the knee, and a lumbar lateral shift. A classification-based approach, mechanical diagnosis and therapy, was utilized to identify the patient with respect to a particular subgroup, and interventions were applied according to symptomatic response to loading strategies, sustained and repeated movements. Outcome measures included the Modified Oswestry Disability Questionnaire (MODQ) and a visual analog scale (VAS) for pain rating. After nine visits (4 weeks), there was a 60% improvement in MODQ score, 0/10 pain on the VAS, and the patient resumed participation in recreational activities. At the 1-year follow-up, there was a 78% overall improvement in MODQ score with continued 0/10 rated pain. Improvements after nine visits and at the 1-year follow-up both exceeded the minimal clinically important difference for the MODQ.

Scale-free Duplication Dynamics: A Model for Ultraduplication

Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics. Dec, 2011  |  Pubmed ID: 22304128

Empirical studies of the genome-wide length distribution of duplicated sequences have revealed an algebraic tail common to nearly all clades. The decay of the tail is often well approximated by a single exponent that takes values within a limited range. We propose and study here scale-free duplication dynamics, a class of model for genome sequence evolution that generates the observed shapes of this distribution. A transition between self-similar and non-self-similar regimes is exhibited. Our model accounts plausibly for the observed form of the algebraic tail, which is not produced by standard models for generating long-range sequence correlations.

Latest Innovations in Air and Electric Handpieces

General Dentistry. Nov, 2011  |  Pubmed ID: 22313912

Relative Performance of Lindgren Multiple-funnel, Intercept Panel, and Colossus Pipe Traps in Catching Cerambycidae and Associated Species in the Southeastern United States

Journal of Economic Entomology. Dec, 2011  |  Pubmed ID: 22299355

In 2004, we evaluated the relative performance of 8-unit Lindgren multiple-funnel (funnel), Intercept panel (panel), and Colossus pipe (pipe) traps, baited with ethanol and ac-pinene lures, in catching saproxylic beetles (Coleoptera) in pine stands in northern Florida and western South Carolina. Panel traps were as good as, if not better than, funnel and pipe traps for catching Cerambycidae. In particular, more Monochamus titillator (F.) were captured in panel traps than in pipe and funnel traps. Of three species of Buprestidae captured in our study, most Buprestis lineata F. were caught in panel traps, whereas most Acmaeodera tubulus (F.) were caught in funnel traps. Catches of Chalcophora virginiensis Drury and the root-feeding weevils Hylobius pales Herbst an dPachylobius picivorus LeConte (Curculionidae) were unaffected by trap type. Among bark beetles (Curculionidae: Scolytinae), catches of Ips grandicollis (Eichhoff) were unaffected by trap type, whereas most Dendroctonus terebrans (Olivier) were caught in panel traps, most Hylastes salebrosus Eichhoff were caught in panel and pipe traps, and most Hylastes tenuis Eichhoff were caught in funnel traps. Among ambrosia beetles (Curculionidae: Scolytinae), panel traps caught the most Xyleborinus saxesenii (Ratzeburg), whereas pipe traps caught the most Xyleborus Eichhoff spp. More Xylosandrus crassiusculus (Motschulsky) and Dryoxylon onoharaensis (Murayama) were caught in panel and funnel traps than in pipe traps. Among bark beetle predators, more Platysoma Leach spp. (Histeridae) were caught in pipe and panel traps than in funnel traps, whereas most Lasconotus Erichson spp. (Zopheridae) were caught in funnel traps. Variation among trap performance for various species suggests that managers should consider more than one type of trap in their detection programs.

High Anemia Prevalence in Western China

The Southeast Asian Journal of Tropical Medicine and Public Health. Sep, 2011  |  Pubmed ID: 22299447

We assessed the prevalence of anemia among schoolchildren in western China as determined by seven cross-sectional surveys involving 12,768 children aged 8-12 years. Subjects were selected randomly from 283 primary schools in 41 economically disadvantaged counties of Ningxia, Qinghai, Shaanxi and Sichuan Provinces. Data were collected through questionnaires and hemoglobin levels were measured. The anemia prevalence was 34% using the WHO hemoglobin cutoff of < 120 g/l. Boarding students and girls were more likely to be anemic. The prevalence of anemia in schoolchildren was high. Iron deficiency is a significant nutrition issue in China.

Serum Levels of the Ovarian Cancer Biomarker HE4 Are Decreased in Pregnancy and Increase with Age

American Journal of Obstetrics and Gynecology. Dec, 2011  |  Pubmed ID: 22301440

OBJECTIVE: The purpose of this study was to establish normal ranges for human epididymis protein 4 (HE4) serum levels in healthy women. STUDY DESIGN: HE4 levels were measured in healthy women and analyzed by age, menopausal status, and pregnancy status. Upper 95th percentiles were determined for normal ranges. RESULTS: Serum samples from 1101 healthy women and 67 pregnant women were analyzed. Above the age of 40 years significant elevations in HE4 concentrations emerged with advancing age. The upper 95th percentile for HE4 levels was 89 pmol/L for premenopausal women, 128 pmol/L for postmenopausal women, and 115 pmol/L for all women. There was a significant difference in the median serum HE4 levels in premenopausal women (46.6 pmol/L) compared with postmenopausal women (57.6 pmol/L; P < .001). In pregnant women, median HE4 concentrations were significantly lower than their premenopausal counterparts (P < .001). CONCLUSION: HE4 serum concentrations vary significantly on the basis of age. These variations must be considered when the upper limit of normal for HE4 is determined.

The Role of Dairy Products in Healthy Weight and Body Composition in Children and Adolescents

Current Nutrition and Food Science. Feb, 2011  |  Pubmed ID: 22299005

Overweight and obesity are major public health concerns with approximately 32% and 17% of U.S. children aged 2 - 19 being classified as overweight or obese, respectively. While the cause of overweight and obesity is multi-factorial, changes in eating habits and physical activity patterns have been proposed as contributing factors to the obesity epidemic. For example, the displacement of nutrient rich foods and beverages with non-nutrient dense items may be influencing childhood obesity. Many children do not consume the recommended servings of the Food Groups to Encourage, i.e. low-fat and fat-free dairy foods, fruits, vegetables, and whole grains identified by the 2005 Dietary Guidelines for Americans which results in low intakes of calcium, potassium, fiber, magnesium, and vitamin E. While attention has focused primarily on reducing energy intake and/or increasing energy expenditure for weight maintenance, a promising beneficial role for dairy products in weight management has emerged. Most research has focused on adults, but there is evidence in children and adolescents indicating either a beneficial or neutral effect of dairy food consumption on body weight or body composition. The current review provides and assessment of the scientific evidence on the effects of dairy food consumption on body weight and body composition in children and adolescents.

Wesley College Ignites Potential with Undergraduate Research Program

Council on Undergraduate Research Quarterly. 2011  |  Pubmed ID: 22303090

Dairy Components and Risk Factors for Cardiometabolic Syndrome: Recent Evidence and Opportunities for Future Research

Advances in Nutrition (Bethesda, Md.). Sep, 2011  |  Pubmed ID: 22332081

Cardiometabolic syndrome (CMS), a cluster of metabolic abnormalities that increases the risk of cardiovascular disease (CVD) and type 2 diabetes, affects over one-third of American adults and accounts for billions of dollars in health care costs annually. Current evidence indicates an inverse association between consumption of dairy foods and risk of CMS and its related disease outcomes. Although the specific mechanism(s) underlying the beneficial effects of dairy consumption on the development of CMS, CVD, and type 2 diabetes have not been fully elucidated, there is evidence that specific components within dairy such as milkfat, vitamin D, calcium, magnesium, potassium, and whey proteins may be individually or collectively involved. Specifically, each of these dairy components has been implicated as having a neutral or beneficial effect on one or more elements of CMS, including the serum lipid profile, blood pressure, fasting glucose, and body composition. Although several mechanisms have been identified by which components in dairy may beneficially affect symptoms associated with CMS, further research is required to better understand how dairy and its components may contribute to metabolic health. The purpose of this review is to present the mechanisms by which specific dairy components modulate risk factors for CMS and identify opportunities for future research.

RAS Mutations and Oncogenesis: Not All RAS Mutations Are Created Equally

Frontiers in Genetics. 2011  |  Pubmed ID: 22303394

Mutation in RAS proteins is one of the most common genetic alterations observed in human and experimentally induced rodent cancers. In vivo, oncogenic mutations have been shown to occur at exons 12, 13, and 61, resulting in any 1 of 19 possible point mutations in a given tumor for a specific RAS isoform. While some studies have suggested a possible role of different mutant alleles in determining tumor severity and phenotype, no general consensus has emerged on the oncogenicity of different mutant alleles in tumor formation and progression. Part of this may be due to a lack of a single, signature pathway that shows significant alterations between different mutations. Rather, it is likely that subtle differences in the activation, or lack thereof, of downstream effectors by different RAS mutant alleles may determine the eventual outcome in terms of tumor phenotype. This paper reviews our current understanding of the potential role of different RAS mutations on tumorigenesis, highlights studies in model cell culture and in vivo systems, and discusses the potential of expression array and computational network modeling to dissect out differences in activated RAS genes in conferring a transforming phenotype.

Sided Functions of an Arginine-Agmatine Antiporter Oriented in Liposomes

Biochemistry. Feb, 2012  |  Pubmed ID: 22304019

The arginine-dependent extreme acid resistance system helps enteric bacteria survive the harsh gastric environment. At the center of this multiprotein system is an arginine-agmatine antiporter, AdiC. To maintain cytoplasmic pH, AdiC imports arginine and exports its decarboxylated product, agmatine, resulting in a net extrusion of one "virtual proton" in each turnover. The random orientation of AdiC in reconstituted liposomes throws up an obstacle to quantifying its transport mechanism. To overcome this problem, we introduced a mutation, S26C, near the substrate-binding site. This mutant exhibits substrate recognition and pH-dependent activity similar to those of the wild-type protein but loses function completely upon reaction with thiol reagents. The membrane-impermeant MTSES reagent can then be used as a cleanly sided inhibitor to silence those S26C-AdiC proteins whose extracellular portion projects from the external side of the liposome. Alternatively, the membrane-permeant MTSEA and membrane-impermeant reducing reagent, TCEP, can be used together to inhibit proteins in the opposite orientation. This approach allows steady-state kinetic analysis of AdiC in a sided fashion. Arginine and agmatine have similar Michaelis-Menten parameters for both sides of the protein, while the extracellular side selects arginine over argininamide, a mimic of the carboxylate-protonated form of arginine, more effectively than does the cytoplasmic side. Moreover, the two sides of AdiC have different pH sensitivities. AdiC activity increases to a plateau at pH 4 as the extracellular side is acidified, while the cytoplasmic side shows an optimal pH of 5.5, with further acidification inhibiting transport. This oriented system allows more precise analysis of AdiC-mediated substrate transport than has been previously available and permits comparison to the situation experienced by the bacterial membrane under acid stress.

What Do We Know About Dietary Fiber Intake in Children and Health? The Effects of Fiber Intake on Constipation, Obesity, and Diabetes in Children

Advances in Nutrition (Bethesda, Md.). Jan, 2012  |  Pubmed ID: 22332100

The effect of dietary fiber intake on chronic diseases has been explored in adults but is largely unknown in children. This paper summarizes the currently existing evidence on the implications of dietary fiber intake on constipation, obesity, and diabetes in children. Current intake studies suggest that all efforts to increase children's dietary fiber consumption should be encouraged. Available data, predominantly from adult studies, indicate significantly lower risks for obesity, diabetes, and constipation could be expected with higher dietary fiber consumption. However, there is a lack of data from clinical studies in children of various ages consuming different levels of dietary fiber to support such assumptions. The existing fiber recommendations for children are conflicting, a surprising situation, because the health benefits associated with higher dietary fiber intake are well established in adults. Data providing conclusive evidence to either support or refute some, if not all, of the current pediatric fiber intake recommendations are lacking. The opportunity to improve children's health should be a priority, because it also relates to their health later in life. The known health benefits of dietary fiber intake, as summarized in this paper, call for increased awareness of the need to examine the potential benefits to children's health through increased dietary fiber.

Prediction of Cognitive Decline by Positron Emission Tomography of Brain Amyloid and Tau

Archives of Neurology. Feb, 2012  |  Pubmed ID: 22332188

To determine whether 2-(1-{6-[(2-fluorine 18-labeled fluoroethyl)methylamino]-2-napthyl}ethylidene) malononitrile ([(18)F]FDDNP) brain regional values in individuals without dementia predict and correlate with future cognitive change.

Biogem: an Effective Tool Based Approach for Scaling Up Open Source Software Development in Bioinformatics

Bioinformatics (Oxford, England). Feb, 2012  |  Pubmed ID: 22332238

SUMMARY: Biogem provides a software development environment for the Ruby programming language, which encourages community-based software development for bioinformatics while lowering the barrier to entry and encouraging best practices.Biogem, with its targeted modular and decentralized approach, software generator, tools, and tight web integration, is an improved general model for scaling up collaborative open source software development in bioinformatics. AVAILABILITY: Biogem and modules are free and open source software. Biogem runs on all systems that support recent versions of Ruby, including Linux, Mac OS X and Windows. Further information at http://www.biogems.info. A tutorial is available at http://www.biogems.info/howto.html CONTACT: Raoul J.P. Bonnal (bonnal@ingm.org).

Modern Technology Calls for a Modern Approach to Classification of Epileptic Seizures and the Epilepsies

Epilepsia. Feb, 2012  |  Pubmed ID: 22332669

In the last 10-15 years the ILAE Commission on Classification and Terminology has been presenting proposals to modernize the current ILAE Classification of Epileptic Seizures and Epilepsies. These proposals were discussed extensively in a series of articles published recently in Epilepsia and Epilepsy Currents. There is almost universal consensus that the availability of new diagnostic techniques as also of a modern understanding of epilepsy calls for a complete revision of the Classification of Epileptic Seizures and Epilepsies. Unfortunately, however, the Commission is still not prepared to take a bold step ahead and completely revisit our approach to classification of epileptic seizures and epilepsies. In this manuscript we critically analyze the current proposals of the Commission and make suggestions for a classification system that reflects modern diagnostic techniques and our current understanding of epilepsy.

Editorial Comment on END-2011-0169-OR.R2

Journal of Endourology / Endourological Society. Feb, 2012  |  Pubmed ID: 22332875

Abstract not indicated for this editorial comment.

Up-regulation of GLT1 Reverses the Deficit in Cortically Evoked Striatal Ascorbate Efflux in the R6/2 Mouse Model of Huntington's Disease

Journal of Neurochemistry. Feb, 2012  |  Pubmed ID: 22332910

A corticostriatal-dependent deficit in the release of ascorbate (AA), an antioxidant vitamin and neuromodulator, occurs concurrently in striatum with dysfunctional GLT1-dependent uptake of glutamate in the R6/2 mouse model of Huntington's disease (HD), an autosomal dominant condition characterized by overt corticostriatal dysfunction. To determine if deficient striatal AA release into extracellular fluid is related to altered GLT1 activity in HD, symptomatic R6/2 mice between 6 and 9 weeks of age and age-matched wild-type (WT) mice received single daily injections of 200 mg/kg ceftriaxone, a β-lactam antibiotic that elevates the functional expression of GLT1, or saline vehicle for 5 consecutive days. On the following day, in vivo voltammetry was coupled with corticostriatal afferent stimulation to monitor evoked release of AA into striatum. In saline-treated mice, we found a marked decrease in evoked extracellular AA in striatum of R6/2 relative to WT. Ceftriaxone, in contrast, restored striatal AA in R6/2 mice to WT levels. In addition, intra-striatal infusion of either the GLT1 inhibitor dihydrokainic acid (DHK) or DL-threo-beta-benzyloxyaspartate (TBOA) blocked evoked striatal AA release. Collectively, our results provide compelling evidence for a link between GLT1 activation and release of AA into the striatal extracellular fluid, and suggest that dysfunction of this system is a key component of HD pathophysiology. © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Laboratory Evaluation of Large-Scale Decontamination Approaches

Journal of Applied Microbiology. Feb, 2012  |  Pubmed ID: 22332972

Aims:  To evaluate the effectiveness of two spray-based decontamination methods for surface contamination reduction and to determine the potential for contamination spread by these methods. Methods and Results:  Material coupons (treated plywood and concrete) were contaminated with ∼1 X 10(7) spores of Bacillus atrophaeus by aerosol deposition. Decontaminants (pH-adjusted bleach or Spor-Klenz® RTU) were applied to coupons by either backpack sprayer or gas-powered sprayer. Contact time, reapplication frequency, and rinse method were also varied. In addition to surface removal efficacy, partitioning of contamination between the rinsate and aerosol fractions was determined. Results indicated that pH-adjusted bleach was effective (≥6 logs reduction) when two applications and a 30 minute contact time were administered, regardless of the decontaminant application method or material. Spor-Klenz® RTU was effective on wood, but achieved ≤3 logs reduction on concrete. A shortened application procedure with pH-adjusted bleach resulted in lower efficacy on wood, and a greater apparent potential for contamination spread. Conclusions:  Consideration of material surface type is important when selecting a decontaminant. Also, achieving conditions that effectively inactivate surface biological contamination are critical to preventing the spread of contamination. Significance and Impact:  Results presented here are intended to help development of remediation plans following a biological contamination incident. © No claim to US Government works. Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

Evidence of Cryptosporidium Transmission Between Cattle and Humans in Northern New South Wales

Experimental Parasitology. Feb, 2012  |  Pubmed ID: 22333036

Cryptosporidium is an enteric parasite of public health significance that causes diarrhoeal illness through faecal oral contamination and via water. Zoonotic transmission is difficult to determine as most species of Cryptosporidium are morphologically identical and can only be differentiated by molecular means. Transmission dynamics of Cryptosporidium in rural populations were investigated through the collection of 196 faecal samples from diarrheic (scouring) calves on 20 farms and 63 faecal samples from humans on 14 of these farms. The overall prevalence of Cryptosporidium in cattle and humans by PCR and sequence analysis of the 18S rRNA was 73.5% (144/196) and 23.8% (15/63), respectively. Three species were identified in cattle; Cryptosporidium parvum, Cryptosporidium bovis and Cryptosporidium ryanae, and from humans, C. parvum and C. bovis. This is only the second report of C. bovis in humans. Subtype analysis at the gp60 locus identified C. parvum subtype IIaA18G3R1 as the most common subtype in calves. Of the seven human C. parvum isolates successfully subtyped, five were IIaA18G3R1, one was IIdA18G2 and one isolate had a mix of IIaA18G3R1 and IIdA19G2. These findings suggest that zoonotic transmission may have occurred but more studies involving extensive sampling of both calves and farm workers are needed for a better understanding of the sources of Cryptosporidium infections in humans from rural areas of Australia.

Carbon Storage of Headwater Riparian Zones in an Agricultural Landscape

Carbon Balance and Management. Feb, 2012  |  Pubmed ID: 22333213

ABSTRACT: BACKGROUND: In agricultural regions, streamside forests have been reduced in age and extent, or removed entirely to maximize arable cropland. Restoring and reforesting such riparian zones to mature forest, particularly along headwater streams (which constitute 90% of stream network length) would both increase carbon storage and improve water quality. Age and management-related cover/condition classes of headwater stream networks can be used to rapidly inventory carbon storage and sequestration potential if carbon storage capacity of conditions classes and their relative distribution on the landscape are known. RESULTS: Based on the distribution of riparian zone cover/condition classes in sampled headwater reaches, current and potential carbon storage was extrapolated to the remainder of the North Carolina Coastal Plain stream network. Carbon stored in headwater riparian reaches is only about 40% of its potential capacity, based on 242 MgC/ha stored in sampled mature riparian forest (forest > 50 y old). The carbon deficit along 57,700 km of headwater Coastal Plain streams is equivalent to about 25TgC in 30-m-wide riparian buffer zones and 50 TgC in 60-m-wide buffer zones. CONCLUSIONS: Estimating carbon storage in recognizable age-and cover-related condition classes provides a rapid way to better inventory current carbon storage, estimate storage capacity, and calculate the potential for additional storage. In light of the particular importance of buffer zones in headwater reaches in agricultural landscapes in ameliorating nutrient and sediment input to streams, encouraging the restoration of riparian zones to mature forest along headwater reaches worldwide has the potential to not only improve water quality, but also simultaneously reduce atmospheric CO2.

Immunogenicity of a Single Dose of Meningococcal Group C Conjugate Vaccine Given at 3 Months of Age to Healthy Infants in the United Kingdom

The Pediatric Infectious Disease Journal. Feb, 2012  |  Pubmed ID: 22333698

BACKGROUND:: From 1999, in the UK, meningococcal C conjugate (MCC) vaccines from 3 manufacturers, were introduced to the infant immunization schedule at 2,3 and 4 months of age. In 2006, the schedule was refined to a two dose primary schedule at 3 and 4 months of age, with a combined MCC/Haemophilus influenzae type b (MCC/Hib-TT) booster at 12 months of age. Recent data have demonstrated that two of the three MCC vaccines showed potential for use as a single priming dose in infancy. METHODS:: A randomized trial was undertaken with two MCC vaccines; one using tetanus toxoid carrier protein (MCC-TT) and one using CRM197 carrier protein (MCC-CRM197). Infants were immunized with MCC at 3 months of age followed by a MCC/Hib-TT booster at 12 months of age. RESULTS:: The serum bactericidal antibody (SBA) geometric mean titers (GMT) one month following a single dose of MCC-TT or MCC-CRM197 were 223.3 (95% CI 162.9-306.1) and 95.8 (95% CI 66.4-138.2) with 100% and 95.5% of infants having SBA titers ≥ 8, respectively. Before boosting, antibody titers had declined and 1 month following MCC/Hib-TT booster, SBA GMTs rose to 2251.0 (95% 1535.3-3300.3) and 355.9 (95% CI 235.4-538.1) for children primed with MCC-TT and MCC-CRM197, respectively. CONCLUSION:: In conclusion, a single priming dose of either MCC-TT or MCC-CRM197 administered at 3 months of age can be used together with the Hib/MCC-TT booster in the second year of life.

One Thing Leads to Another: the Cascade of Obligations when Researchers Report Genetic Research Results to Study Participants

European Journal of Human Genetics : EJHG. Feb, 2012  |  Pubmed ID: 22333903

Even as debate continues about the putative obligation to proactively report genetic research results to study participants, there is an increasing need to attend to the obligations that might cascade from any initial report. We conducted an international, quasi-experimental survey of researchers involved in autism spectrum disorders (ASD) and cystic fibrosis (CF) genetics to explore perceived obligations to ensure updated information or relevant clinical care subsequent to any initial communication of research results, and factors influencing these attitudes. 5-point Likert scales of dis/agreement were analyzed using descriptive and multivariate statistics. Of the 343 respondents (44% response rate), large majorities agreed that in general and in a variety of hypothetical research contexts, research teams that report results should ensure that participants gain subsequent access to updated information (74-83%) and implicated clinical services (79-87%). At the same time, researchers perceived barriers restricting access to relevant clinical care, though this was significantly more pronounced (P<0.001) for ASD (64%) than CF (34%). In the multivariate model, endorsement of cascading obligations was positively associated with researcher characteristics (eg, clinical role/training) and attitudes (eg, perceived initial reporting obligation), and negatively associated with the initial report of less scientifically robust hypothetical results, but unaffected by perceived or hypothetical barriers to care. These results suggest that researchers strongly endorse information and care-based obligations that cascade from the initial report of research results to study participants. In addition, they raise challenging questions about how any cascading obligations are to be met, especially where access challenges are already prevalent.European Journal of Human Genetics advance online publication, 15 February 2012; doi:10.1038/ejhg.2012.24.

FLOWERING BHLH Transcriptional Activators Control Expression of the Photoperiodic Flowering Regulator CONSTANS in Arabidopsis

Proceedings of the National Academy of Sciences of the United States of America. Feb, 2012  |  Pubmed ID: 22334645

Many plants monitor day-length changes throughout the year and use the information to precisely regulate the timing of seasonal flowering for maximum reproductive success. In Arabidopsis thaliana, transcriptional regulation of the CONSTANS (CO) gene and posttranslational regulation of CO protein are crucial mechanisms for proper day-length measurement in photoperiodic flowering. Currently, the CYCLING DOF FACTOR proteins are the only transcription factors known to directly regulate CO gene expression, and the mechanisms that directly activate CO transcription have remained unknown. Here we report the identification of four CO transcriptional activators, named FLOWERING BHLH 1 (FBH1), FBH2, FBH3, and FBH4. All FBH proteins are related basic helix-loop-helix-type transcription factors that preferentially bind to the E-box cis-elements in the CO promoter. Overexpression of all FBH genes drastically elevated CO levels and caused early flowering regardless of photoperiod, whereas CO levels were reduced in the fbh quadruple mutants. In addition, FBH1 is expressed in the vascular tissue and bound near the transcription start site of the CO promoter in vivo. Furthermore, FBH homologs in poplar and rice induced CO expression in Arabidopsis. These results indicate that FBH proteins positively regulate CO transcription for photoperiodic flowering and that this mechanism may be conserved in diverse plant species. Our results suggest that the diurnal CO expression pattern is generated by a concert of redundant functions of positive and negative transcriptional regulators.

Parsimony in Personality: Predicting Sexual Prejudice

Journal of Homosexuality. Feb, 2012  |  Pubmed ID: 22335418

Extant research has established numerous demographic, personal-history, attitudinal, and ideological correlates of sexual prejudice, also known as homophobia. The present study investigated whether Five-Factor Model (FFM) personality domains, particularly Openness, and FFM facets, particularly Openness to Values, contribute independent and incremental variance to the prediction of sexual prejudice beyond these established correlates. Participants were 117 college students who completed a comprehensive FFM measure, measures of sexual prejudice, and a demographics, personal-history, and attitudes-and-ideologies questionnaire. Results of stepwise multiple regression analyses demonstrated that, whereas Openness domain score predicted only marginal incremental variance in sexual prejudice, Openness facet scores (particularly Openness to Values) predicted independent and substantial incremental variance beyond numerous other zero-order correlates of sexual prejudice. The importance of integrating FFM personality variables, especially facet-level variables, into conceptualizations of sexual prejudice is highlighted. Study strengths and weaknesses are discussed as are potential implications for prejudice-reduction interventions.

Spontaneous Operational Tolerance in Kidney Transplant Recipients

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. Feb, 2012  |  Pubmed ID: 22335537

Self-reported Memory Impairment and Brain PET of Amyloid and Tau in Middle-aged and Older Adults Without Dementia

International Psychogeriatrics / IPA. Feb, 2012  |  Pubmed ID: 22335970

ABSTRACTBackground: Whether perceived changes in memory parallel changes in brain pathology is uncertain. Positron emission tomography (PET) scans using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP) can measure levels of amyloid plaques and tau neurofibrillary tangles in vivo. Here we investigate whether degree of self-reported memory impairment is associated with FDDNP-PET binding levels in persons without dementia.Methods: Fifty-seven middle-aged and older adults without dementia (mean age ±standard deviation = 66.3 ± 10.6 years), including 25 with normal aging and 32 with mild cognitive impairment (MCI), were assessed. The outcome measures were the four factor scores of the Memory Functioning Questionnaire (MFQ) (frequency of forgetting, seriousness of forgetting, retrospective functioning, and mnemonics use) and FDDNP-PET binding levels in medial temporal, lateral temporal, posterior cingulate, parietal, frontal, and global (overall average) regions of interest.Results: After controlling for age, higher reported frequency of forgetting was associated with greater medial temporal (r = -0.29, p = 0.05), parietal (r = -0.30, p = 0.03), frontal (r = -0.35, p = 0.01), and global FDDNP-PET binding levels (r = -0.33, p = 0.02). The remaining MFQ factor scores were not significantly associated with FDDNP-PET binding levels, and no significant differences were found between normal aging and MCI subjects. Item analysis of the frequency of forgetting factor revealed five questions that yielded similar results as the full 32-question scale (r = -0.52, p = 0.0002).Conclusions: These findings suggest that some forms of memory self-awareness, in particular the reported frequency of forgetting, may reflect the extent of cerebral amyloid and tau brain pathology.

Influence of Maternal Asthma on the Cause and Severity of Infant Acute Respiratory Tract Infections

The Journal of Allergy and Clinical Immunology. Feb, 2012  |  Pubmed ID: 22336082

BACKGROUND: Respiratory syncytial virus (RSV) and rhinovirus infections are the most common significant infant respiratory tract illnesses and are associated with increased but differential risks of childhood asthma. OBJECTIVE: We sought to determine whether maternal asthma is associated with higher odds of infant respiratory tract infection with rhinovirus versus RSV and increased infection severity. METHODS: Mother-infant dyads were enrolled from 2004-2008 during an infant respiratory tract infection (104 with rhinovirus and 279 with RSV). Mothers were classified into mutually exclusive groups (atopic asthma, nonatopic asthma, and no asthma). We determined viral cause using PCR and the severity of the infant's respiratory tract infection using the bronchiolitis severity score. Adjusted relative odds of maternal asthma with viral cause were calculated by using logistic regression. Proportional odds models assessed the association of maternal asthma and infant infection severity. RESULTS: Infants with a mother with atopic asthma compared with infants whose mothers did not have asthma were more likely to have rhinovirus versus RSV infection (adjusted odds ratio, 2.42; 95% CI, 1.19-4.90). Similarly, among infants with rhinovirus, having a mother with atopic asthma was associated with increased infection severity (adjusted odds ratio, 3.10; 95% CI, 1.21-7.98). This relationship was not seen among infants with RSV. CONCLUSIONS: Clinically significant rhinovirus infection during infancy was more strongly associated with having a mother with atopic asthma than clinically significant RSV infection. Having a mother with atopic asthma was associated with increased severity of infant rhinovirus but not RSV infections. Infants with rhinovirus were more likely to have a familial atopic predisposition, which might partly explain the subsequent increased asthma risk.

Prediction of Weight Loss and Regain Following Dietary, Lifestyle, and Pharmacologic Intervention

Clinical Pharmacology and Therapeutics. Feb, 2012  |  Pubmed ID: 22336590

To develop statistical models for predicting weight loss and regain, we analyzed the phenotypic responses in an outpatient study of 60 obese subjects randomized to one of three 12-week interventions, diet (-600 kcal) alone, diet with exercise, and diet with sibutramine. This was followed by 12 weeks of observation. The best of the "baseline covariates" models was one that incorporated intervention group and baseline homeostasis model assessment-estimated insulin resistance (HOMA(IR)). It predicted week 12 weight change with R(2) of 0.38 and root mean square error (√MSE) of 2.92 kg. An alternative model incorporating baseline fat mass plus change in weight and HOMA(IR) at week 4 improved the prediction (R(2), 0.67, √MSE, 2.19 kg). We could not identify a satisfactory model to predict weight regain. We conclude that prediction of weight loss over 12 weeks is significantly improved when short-term weight change is incorporated into the model. This information could be utilized to forecast the success of a weight-loss program and to motivate and contribute to innovative designing of obesity trials.

Bronchial Nitric Oxide Flux May Be Better Associated with Inducible Nitric Oxide Synthase Promoter Methylation

American Journal of Respiratory and Critical Care Medicine. Feb, 2012  |  Pubmed ID: 22336683

Telomere Proteins POT1, TRF1 and TRF2 Augment Long-patch Base Excision Repair in Vitro

Cell Cycle (Georgetown, Tex.). Mar, 2012  |  Pubmed ID: 22336916

Human telomeres consist of multiple tandem hexameric repeats, each containing a guanine triplet. Guanosine-rich clusters are highly susceptible to oxidative base damage, necessitating base excision repair (BER). Previous demonstration of enhanced strand displacement synthesis by the BER component DNA polymerase β in the presence of telomere protein TRF2 suggests that telomeres employ long-patch (LP) BER. Earlier analyses in vitro showed that efficiency of BER reactions is reduced in the DNA-histone environment of chromatin. Evidence presented here indicates that BER is promoted at telomeres. We found that the three proteins that contact telomere DNA, POT1, TRF1 and TRF2, enhance the rate of individual steps of LP-BER and stimulate the complete reconstituted LP-BER pathway. Thought to protect telomere DNA from degradation, these proteins still apparently evolved to allow selective access of repair proteins.

Identifying Polyglutamine Protein Species in Situ That Best Predict Neurodegeneration

Nature Chemical Biology. 2012  |  Pubmed ID: 22337097

The Effects of Intrauterine Growth Restriction and Antenatal Glucocorticoids on Ovine Fetal Lung Development

Pediatric Research. Feb, 2012  |  Pubmed ID: 22337223

Intrauterine fetal growth restriction (IUGR) is associated with high rates of neonatal morbidity. IUGR babies are often born preterm and are therefore exposed to antenatal glucocorticoids. Antenatal glucocorticoids significantly improve overall survival rates of preterm infants, but there is a paucity of information about their effects on IUGR infants. We induced IUGR in sheep by single umbilical artery ligation (SUAL), or sham in control fetuses. To half the ewes, we administered betamethasone (BM) on days 5 (BM1) and 6 (BM2) following surgery and collected fetal lung tissue on day 7. SUAL alone was associated with higher circulating fetal cortisol levels (2.8±0.4 vs 1.0±0.4, P=0.001) compared to controls, but no changes in lung morphology or surfactant protein (SP) gene expression. BM was associated with a significant reduction in lung tissue density (P=0.048). There were no significant differences between groups in lung DNA concentration or septal crest density. SP-A, -B and -C gene expression was significantly increased in control and SUAL fetuses given BM. These results show that in SUAL fetuses, maternal betamethasone is associated with acceleration of fetal lung structure, as occurs in normally grown fetuses, and that betamethasone induces SP production, an effect not observed in SUAL-induced IUGR fetuses alone.

Predictors and Outcomes of Pneumonia in Patients With Spontaneous Intracerebral Hemorrhage

Journal of Intensive Care Medicine. Feb, 2012  |  Pubmed ID: 22337709

Objectives. Pneumonia is an important complication of spontaneous intracerebral hemorrhage (sICH). The purpose of this study was to determine the predictors and outcomes of the development of pneumonia in patients with sICH. Methods. In total, 290 consecutive patients with sICH admitted within 24 hours of stroke onset were investigated in a single center, retrospective study from January 2006 to July 2009. Clinical, biochemical, and imaging variables were registered. Stroke severity and functional outcomes were evaluated with the Glasgow Coma Scale (GCS) and modified Rankin Scale (mRS). Baseline variables that predicted pneumonia were investigated and outcomes were assessed. Results. The association of our primary exposure variables, such as mechanical ventilation, tube feeding, dysphagia, and tracheostomy, with pneumonia was highly significant (P < .0001, for each variable). For mechanical ventilation, we observed an odds ratio (OR; 95% confidence interval [CI]) of 9.42 (4.24-20.9); for tube feeding, OR = 22.3 (8.91-55.8); for dysphagia, OR = 13.1 (4.66-36.7); and for tracheostomy, OR = 26.8 (8.02-89.3). After adjustment of potential confounders including GCS and mRS on admission, the use of angiotensin-converting enzyme inhibitors, proton pump inhibitors, and H2 blockers, all the adjusted OR (ORa) remained significant. For mechanical ventilation, the minimum ORa was 3.72 (95% CI: 1.68-8.26) when adjusted for GCS. For both dysphagia and tracheostomy, mRS reduced OR to 7.46 (95% CI: 3.34-10.6) in the case of dysphagia with an ORa of 16.2 (95% CI: 4.98 to 52.8) for tracheostomy. For tube feeding, both GCS and mRS reduced ORa; the former to 14.7 (95% CI: 6.16-35.0) and the latter to 15.7 (95% CI: 6.63-37.0). Pneumonia shows a significant effect on the morbidity (P = .003), length of stay (P < .0001), and mortality (P = .041) rate of the patients. Conclusion. Mechanical ventilation, tube feeding, dysphagia, and tracheostomy are exposures associated with increased risk of the development of pneumonia in patients with sICH. Pneumonia is associated with an increase in morbidity, length of stay, and mortality among patients with sICH.

How the Moralization of Issues Grants Social Legitimacy to Act on One's Attitudes

Personality & Social Psychology Bulletin. Feb, 2012  |  Pubmed ID: 22337765

Actions that do not have as their goal the advancement or protection of one's material interests are often seen as illegitimate. Four studies suggested that moral values can legitimate action in the absence of material interest. The more participants linked sociopolitical issues to moral values, the more comfortable they felt advocating on behalf of those issues and the less confused they were by others' advocacy (Studies 1 and 2). Crime victims were perceived as being more entitled to claim special privileges when the crime had violated their personal moral values (Studies 3 and 4). These effects were strongest when the legitimacy to act could not already be derived from one's material interests, suggesting that moral values and material interest can represent interchangeable justifications for behavior. No support was found for the possibility that attitude strength explained these effects. The power of moralization to disinhibit action is discussed.

Ganciclovir-resistant CMV Retinitis in a Patient with Wild-type Plasma CMV

Journal of Clinical Microbiology. Feb, 2012  |  Pubmed ID: 22337988

A patient with systemic CMV, including chorioretinitis, received localized and systemic ganciclovir, systemic cidofivir analog and localized foscarnet. Mutations conferring ganciclovir and cidofivir resistance were detected from the aqueous fluid CMV but not the plasma CMV. Quantifying CMV from aqueous fluid was valuable for monitoring clinical response and predicting resistance.

Money, Coercion, and Undue Inducement: Attitudes About Payments to Research Participants

IRB. Jan-Feb, 2012  |  Pubmed ID: 22338401

A Troglomorphic Spider from Java (Araneae, Ctenidae, Amauropelma)

ZooKeys. 2012  |  Pubmed ID: 22303127

A new troglomorphic spider from caves in Central Java, Indonesia, is described and placed in the ctenid genus Amauropelma Raven, Stumkat & Gray, until now containing only species from Queensland, Australia. Only juveniles and mature females of the new species are known. We give our reasons for placing the new species in Amauropelma, discuss conflicting characters, and make predictions about the morphology of the as yet undiscovered male that will test our taxonomic hypothesis. The description includes DNA barcode sequence data.

TRIM32 Regulates Skeletal Muscle Stem Cell Differentiation and Is Necessary for Normal Adult Muscle Regeneration

PloS One. 2012  |  Pubmed ID: 22299041

Limb girdle muscular dystrophy type 2H (LGMD2H) is an inherited autosomal recessive disease of skeletal muscle caused by a mutation in the TRIM32 gene. Currently its pathogenesis is entirely unclear. Typically the regeneration process of adult skeletal muscle during growth or following injury is controlled by a tissue specific stem cell population termed satellite cells. Given that TRIM32 regulates the fate of mammalian neural progenitor cells through controlling their differentiation, we asked whether TRIM32 could also be essential for the regulation of myogenic stem cells. Here we demonstrate for the first time that TRIM32 is expressed in the skeletal muscle stem cell lineage of adult mice, and that in the absence of TRIM32, myogenic differentiation is disrupted. Moreover, we show that the ubiquitin ligase TRIM32 controls this process through the regulation of c-Myc, a similar mechanism to that previously observed in neural progenitors. Importantly we show that loss of TRIM32 function induces a LGMD2H-like phenotype and strongly affects muscle regeneration in vivo. Our studies implicate that the loss of TRIM32 results in dysfunctional muscle stem cells which could contribute to the development of LGMD2H.

Methamphetamine Abuse and Oral Health: A Pilot Study of "meth Mouth"

Quintessence International (Berlin, Germany : 1985). Mar, 2012  |  Pubmed ID: 22299123

Abuse of methamphetamine (meth), a potent central nervous system stimulant, has been associated with significant dental disease. Current descriptions of "meth mouth" are limited in their scope and fail to illuminate the potential pathogenic mechanisms of meth for oral disease. The purpose of this pilot study was to characterize the oral health of subjects with a history of meth abuse as compared to nonabusing control subjects. A total of 28 meth abusers and 16 control subjects were enrolled. Interviews and surveys regarding meth abuse, dental history, oral hygiene, and diet were collected. A comprehensive oral cavity examination including salivary characterization was completed. We observed significantly higher rates of decayed surfaces, missing teeth, tooth wear, plaque, and calculus among meth abusers. No significant difference in salivary flow rates were noted, yet results showed significant trends for lower pH and decreased buffering capacity. These findings suggest that salivary quality may play a more important role in meth mouth than previously considered. Salivary analysis may be useful when managing a dental patient with history of methamphetamine abuse. Quintessence Int 2012;43:229-237.

Presence of Interferon-α at the Time of Infection Alters the Innate and Adaptive Immune Response to Porcine Reproductive and Respiratory Syndrome Virus

Clinical and Vaccine Immunology : CVI. Feb, 2012  |  Pubmed ID: 22301694

Porcine reproductive and respiratory syndrome (PRRS) is one of the most devastating and costly diseases to the swine industry world-wide. Overall, the adaptive immune response to PRRS virus (PRRSV) is weak, which results in delayed elimination of virus from the host and inferior vaccine protection. PRRSV has been shown to induce a meager interferon (IFN)-α response, and we hypothesized that elevated IFN-α levels early in infection would shorten the induction time and increase elements of the adaptive immune response. To test this, we measured both antibody and cell mediated immunity in pigs after the administration of a nonreplicating human adenovirus type 5 vector expressing porcine IFN-α (Ad5-pIFN-α) at the time of PRSSV infection as compared to pigs infected with PRRSV alone. Viremia was delayed and there was a decrease in viral load in the sera of pigs administered the Ad5-pIFN-α. Although seroconversion was slightly delayed in pigs receiving Ad5-pIFN-α, probably due to the early reduction in viral replication, little difference was seen in the overall or neutralizing antibody response. However, there was an increase in the number of virus-specific IFN-γ secreting cells detected in the pigs receiving Ad5-pIFN-α, as well as an altered cytokine profile in the lung 14 days post-infection, indicating that the presence of IFN-α at the time of infection can alter innate and adaptive immune responses to PRRSV.

Microfluidic Nanoplasmonic-enabled Device for Multiplex DNA Detection

Lab on a Chip. Feb, 2012  |  Pubmed ID: 22301735

We describe a rapid, quantitative, multiplex, self-labelled, and real-time DNA biosensor employing Ag nanoparticle-bound DNA hairpin probes immobilized in a microfluidic channel. Capture of complementary target DNAs by the microarrayed DNA hairpin probes results in a positive fluorescence signal via a conformational change of the probe molecules, signalling the presence of target DNAs. The device's capability for quantitative analyses was evaluated and a detection time as low as 6 min (with a target flow rate of 0.5 μl min(-1)) was sufficient to generate significant detection signals. This detection time translates to merely 3 μl of target solution consumption. An unoptimized sensitivity of 500 pM was demonstrated for this device.

Lyme Disease in a British Referral Clinic

QJM : Monthly Journal of the Association of Physicians. Feb, 2012  |  Pubmed ID: 22301822

BACKGROUND: Concerns about over-diagnosis and inappropriate management of Lyme disease (LD) are well documented in North America and supported by clinical data. There are few parallel data on the situation in the UK. AIM: To describe the patterns of referral, investigation, diagnosis and treatment of patients with suspected LD referred to an infectious disease unit in Liverpool, UK. Previous management by National Health Service (NHS) and non-NHS practitioners was reviewed. DESIGN: Descriptive study conducted by retrospective casenotes review. METHODS: Retrospective casenotes review of adults referred with possible LD to an infectious disease unit in Liverpool, UK, over 5 years (2006-2010). RESULTS: Of 115 patients, 27 (23%) were diagnosed with LD, 38 (33%) with chronic fatigue syndrome (CFS) and 13 (11%) with other medical conditions. No specific diagnosis could be made in 38 (33%). At least 53 unnecessary antibiotic courses had been given by non-NHS practitioners; 21 unnecessary courses had been prescribed by NHS practitioners. Among 38 patients, 17 (45%) with CFS had been misdiagnosed as having LD by non-NHS practitioners. CONCLUSION: A minority of referred patients had LD, while a third had CFS. LD is over-diagnosed by non-specialists, reflecting the complexities of clinical and/or laboratory diagnosis. Patients with CFS were susceptible to misdiagnosis in non-NHS settings, reinforcing concerns about missed opportunities for appropriate treatment for this group and about the use of inappropriate diagnostic modalities and anti-microbials in non-NHS settings.

It Takes Two to Transport, or is It One?

Nature Structural & Molecular Biology. 2012  |  Pubmed ID: 22301872

Effect of Increasing Protein Content of Human Milk Fortifier on Growth in Preterm Infants Born at <31 Wk Gestation: a Randomized Controlled Trial

The American Journal of Clinical Nutrition. Feb, 2012  |  Pubmed ID: 22301933

BACKGROUND: Preterm human milk-fed infants often experience suboptimal growth despite the use of human milk fortifier (HMF). The extra protein supplied in fortifiers may be inadequate to meet dietary protein requirements for preterm infants. OBJECTIVE: We assessed the effect of human milk fortified with a higher-protein HMF on growth in preterm infants. DESIGN: This is a randomized controlled trial in 92 preterm infants born at <31 wk gestation who received maternal breast milk that was fortified with HMF containing 1.4 g protein/100 mL (higher-protein group) or 1.0 g protein/100 mL (current practice) until discharge or estimated due date, whichever came first. The HMFs used were isocaloric and differed only in the amount of protein or carbohydrate. Length, weight, and head-circumference gains were assessed over the study duration. RESULTS: Length gains did not differ between the higher- and standard-protein groups (mean difference: 0.06 cm/wk; 95% CI: -0.01, 0.12 cm/wk; P = 0.08). Infants in the higher-protein group achieved a greater weight at study end (mean difference: 220 g; 95% CI: 23, 419 g; P = 0.03). Secondary analyses showed a significant reduction in the proportion of infants who were less than the 10th percentile for length at the study end in the higher-protein group (risk difference: 0.186; 95% CI: 0.370, 0.003; P = 0.047). CONCLUSIONS: A higher protein intake results in less growth faltering in human milk-fed preterm infants. It is possible that a higher-protein fortifier than used in this study is needed. This trial was registered with the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au/) as ACTRN12606000525583.

R179H Mutation in ACTA2 Expanding the Phenotype to Include Prune-belly Sequence and Skin Manifestations

American Journal of Medical Genetics. Part A. Feb, 2012  |  Pubmed ID: 22302747

Mutations in ACTA2 (smooth muscle cell-specific isoform of α-actin) lead to a predisposition to thoracic aortic aneurysms and other vascular diseases. More recently, the ACTA2 R179H mutation has been described in individuals with global smooth muscle dysfunction. We report a patient heterozygous for the mutation in ACTA2 R179H who presented with megacystis at 13 weeks gestational age and, at birth, with prune-belly sequence. He also had deep skin dimples and creases on his palms and soles, a finding not previously described but possibly related to ACTA2. To our knowledge, this is the first report of the R179H mutation in ACTA2 in a child with prune-belly sequence. We think the R179H mutation in ACTA2 should be included in the differential diagnosis of individuals presenting with the sequence without an identified mechanical obstruction. Furthermore, as ACTA2 R179H has been reported in patients with severe vasculomyopathy and premature death, we recommend that molecular testing for this mutation be considered in fetuses presenting with fetal megacystis with a normal karyotype, particularly if the bladder diameter is 15 mm or more, to allow expectant parents to make an informed decision. © 2012 Wiley Periodicals, Inc.

New View of the ICN A Continuum Using Photoelectron Spectroscopy of ICN(-)

The Journal of Chemical Physics. Jan, 2012  |  Pubmed ID: 22299877

Negative-ion photoelectron spectroscopy of ICN(-) (X̃ (2)Σ(+)) reveals transitions to the ground electronic state (X̃ (1)Σ(+)) of ICN as well as the first five excited states ((3)Π(2), (3)Π(1), Π(0(-) ) (3), Π(0(+) ) (3), and (1)Π(1)) that make up the ICN A continuum. By starting from the equilibrium geometry of the anion, photoelectron spectroscopy characterizes the electronic structure of ICN at an elongated I-C bond length of 2.65 Å. Because of this bond elongation, the lowest three excited states of ICN ((3)Π(2), (3)Π(1), and Π(0(-) ) (3)) are resolved for the first time in the photoelectron spectrum. In addition, the spectrum has a structured peak that arises from the frequently studied conical intersection between the Π(0(+) ) (3) and (1)Π(1) states. The assignment of the spectrum is aided by MR-SO-CISD calculations of the potential energy surfaces for the anion and neutral ICN electronic states, along with calculations of the vibrational levels supported by these states. Through thermochemical cycles involving spectrally narrow transitions to the excited states of ICN, we determine the electron affinity, EA(ICN), to be 1.34(5) (+0.04∕-0.02) eV and the anion dissociation energy, D(0)(X̃ (2)Σ(+) I-CN(-)), to be 0.83 (+0.04∕-0.02) eV.

Characterization of Asthma Exacerbations in Primary Care Using Cluster Analysis

The Journal of Asthma : Official Journal of the Association for the Care of Asthma. Mar, 2012  |  Pubmed ID: 22300042

Rationale. Patients with a history of asthma exacerbations are at a higher risk for future episodes of severe asthma exacerbations. Characterization of asthma phenotypes could help improve asthma management, including reducing exacerbations. Aim. The aim of this study is to identify distinctive patient characteristics associated with a history of asthma exacerbations using cluster analysis. Methods. We used data assessing asthma control from two cross-sectional surveys of adult and pediatric patients in the primary care setting. A supervised cluster analysis with recursive partitioning approach was applied to identify characteristics that maximized the differences across subgroups. Results. The sample comprised 2205 adults and 2435 children and adolescents with asthma. Key predictors were identified in seven adult clusters including visiting an asthma specialist, number of hours worked, and excessive use of rescue medication. The rate ratio (RR) for having an exacerbation was significantly higher (2.88; 95% confidence interval (CI), 2.46-3.36) in Cluster 7, with more female patients reporting severe disease, high body mass index, sinus infections, gastroesophageal reflux disease, skin allergies, and lower asthma control score. Features identified in the six pediatric clusters included visiting an asthma specialist, missed school days, race/ethnicity, and age. The RR for having an exacerbation was higher in Cluster 6 (2.36; 95% CI, 2.11-2.64), with patients reporting more severe disease, sinus and skin allergies, and lower asthma control score. Conclusions. Identification of specific risk factors can be enhanced by using supervised cluster analysis. This approach allows grouping of patients with unique characteristics to help identify patients at higher risk of exacerbations.

Re'COG'nition at the Golgi

Traffic (Copenhagen, Denmark). Feb, 2012  |  Pubmed ID: 22300173

The conserved oligomeric Golgi (COG) complex co-ordinates retrograde vesicle transport within the Golgi. These vesicles maintain the distribution of glycosylation enzymes between the Golgi's cisternae, and therefore COG is intimately involved in glycosylation homeostasis. Recent years have greatly enhanced our knowledge of COG's composition, protein interactions, cellular function, and most recently also its structure. The emergence of COG-dependent human glycosylation disorders gives particular relevance to these advances. The structural data have firmly placed COG in the family of multi-subunit tethering complexes that it shares with the exocyst, Dls1 and GARP/VFT complexes. Here we review our knowledge of COG's involvement in vesicle tethering at the Golgi. In particular we consider what this knowledge may add to our molecular understanding of vesicle tethering, and how it impacts on the fine tuning of Golgi function, most notably glycosylation.

Direct Experimental Evidence That Early-life Farm Environment Influences Regulation of Immune Responses

Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology. Feb, 2012  |  Pubmed ID: 22300455

To cite this article: Lewis MC, Inman CF, Patel D, Schmidt B, Mulder I, Miller B, Gill BP, Pluske J, Kelly D, Stokes CR, Bailey M. Direct experimental evidence that early-life farm environment influences regulation of immune responses. Pediatr Allergy Immunol 2011: doi: 10.1111/j.1399-3038.2011.01258.x. ABSTRACT: Background:  In mammals, early-life environmental variations appear to affect microbial colonization and therefore competent immune development, and exposure to farm environments in infants has been inversely correlated with allergy development. Modelling these effects using manipulation of neonatal rodents is difficult due to their dependency on the mother, but the relatively independent piglet is increasingly identified as a valuable translational model for humans. This study was designed to correlate immune regulation in piglets with early-life environment. Methods:  Piglets were nursed by their mother on a commercial farm, while isolator-reared siblings were formula fed. Fluorescence immunohistology was used to quantify T-reg and effector T-cell populations in the intestinal lamina propria and the systemic response to food proteins was quantified by capture ELISA. Results:  There was more CD4(+) and CD4(+) CD25(+) effector T-cell staining in the intestinal mucosa of the isolator-reared piglets compared with their farm-reared counterparts. In contrast, these isolator-reared piglets had a significantly reduced CD4(+) CD25(+) Foxp3(+) regulatory T-cell population compared to farm-reared littermates, resulting in a significantly higher T-reg-to-effector ratio in the farm animals. Consistent with these findings, isolator-reared piglets had an increased serum IgG anti-soya response to novel dietary soya protein relative to farm-reared piglets. Conclusion:  Here, we provide the first direct evidence, derived from intervention, that components of the early-life environment present on farms profoundly affects both local development of regulatory components of the mucosal immune system and immune responses to food proteins at weaning. We propose that neonatal piglets provide a tractable model which allows maternal and treatment effects to be statistically separated.

In Vivo Detection of Oxidation-specific Epitopes in Atherosclerotic Lesions Using Biocompatible Manganese Molecular Magnetic Imaging Probes

Journal of the American College of Cardiology. Feb, 2012  |  Pubmed ID: 22300697

This study sought to evaluate the in vivo magnetic resonance imaging (MRI) efficacy of manganese [Mn(II)] molecular imaging probes targeted to oxidation-specific epitopes (OSE).

VarScan 2: Somatic Mutation and Copy Number Alteration Discovery in Cancer by Exome Sequencing

Genome Research. Feb, 2012  |  Pubmed ID: 22300766

Cancer is a disease driven by genetic variation and mutation. Exome sequencing can be utilized for discovering these variants and mutations across hundreds of tumors. Here we present an analysis tool, VarScan 2, for the detection of somatic mutations and copy number alterations (CNAs) in exome data from tumor-normal pairs. Unlike most current approaches, our algorithm reads data from both samples simultaneously; a heuristic and statistical algorithm detects sequence variants and classifies them by somatic status (germline, somatic, or LOH); while a comparison of normalized read depth delineates relative copy number changes. We apply these methods to the analysis of exome sequence data from 151 high-grade ovarian tumors characterized as part of the Cancer Genome Atlas (TCGA). We validated some 7790 somatic coding mutations, achieving 93% sensitivity and 85% precision for single nucleotide variant (SNV) detection. Exome-based CNA analysis identified 29 large-scale alterations and 619 focal events per tumor on average. As in our previous analysis of these data, we observed frequent amplification of oncogenes (e.g., CCNE1, MYC) and deletion of tumor suppressors (NF1, PTEN, and CDKN2A). We searched for additional recurrent focal CNAs using the correlation matrix diagonal segmentation (CMDS) algorithm, which identified 424 significant events affecting 582 genes. Taken together, our results demonstrate the robust performance of VarScan 2 for somatic mutation and CNA detection and shed new light on the landscape of genetic alterations in ovarian cancer.

ER Cargo Properties Specify a Requirement for COPII Coat Rigidity Mediated by Sec13p

Science (New York, N.Y.). Feb, 2012  |  Pubmed ID: 22300850

Eukaryotic secretory proteins exit the endoplasmic reticulum via transport vesicles generated by the essential COPII coat proteins. The outer coat complex, Sec13-Sec31, forms a scaffold that is thought to enforce curvature. By exploiting yeast bypass-of-sec-thirteen (bst) mutants, where Sec13p is dispensable, we probed the relationship between a compromised COPII coat and the cellular context in which it could still function. Genetic and biochemical analyses suggested that Sec13p was required to generate vesicles from membranes that contained asymmetrically distributed cargoes that were likely to confer opposing curvature. Thus, Sec13p may rigidify the COPII cage and increase its membrane-bending capacity; this function could be bypassed when a bst mutation renders the membrane more deformable.

Reaction Time As a Measure of Human Associative Learning

Behavioural Processes. Jan, 2012  |  Pubmed ID: 22301095

Studies of human associative learning have often used causal/predictive learning preparations in which participants decide whether or not a first event is effective in causing or predicting a second event (i.e., an outcome). Those preparations have proved successful in replicating many Pavlovian phenomena. In the present paper we tested a novel associative learning preparation in which visually presented letters were paired with a visual outcome. Reaction times (RTs) were recorded to assess associative strength between specific cues and the outcome. Combining two different dependent variables (RTs and type of response given), we propose a rule for evaluating the associative strength between two events. The preparation and the data transformation rule were successful in producing several Pavlovian phenomena including excitatory acquisition, extinction, overshadowing, and latent inhibition, as well as established summation effects. Advantages and limitations of this new preparation based on the use of RT are discussed.

CHARACTERIZATION OF THE 55 RESIDUE PROTEIN ENCODED BY THE 9S E1A MRNA OF SPECIES C ADENOVIRUS

Journal of Virology. Feb, 2012  |  Pubmed ID: 22301148

Early region 1A (E1A) of Human Adenovirus (HAdV) has been the focus of over 30 years of investigation and is required for the oncogenic capacity of HAdV in rodents. Alternative splicing of the E1A transcript generates mRNAs encoding multiple E1A proteins. The 55 residue (55R) E1A protein, which is encoded by the 9S mRNA, is particularly interesting due to the unique properties it displays relative to all other E1A isoforms. 55R E1A does not contain any of the conserved regions (CRs) present in the other E1A isoforms. The C-terminal region of the 55R E1A protein contains a unique sequence compared to all other E1A isoforms, which results from a frameshift generated by alternative splicing. The 55R E1A protein is thought to be preferentially produced at the late stages of infection. Here we report the first study to directly investigate the function of the species C HAdV 55R E1A protein during infection. Polyclonal rabbit antibodies (Abs) have been generated that are capable of immunoprecipitating HAdV-2 55R E1A. These Abs can also detect HAdV-2 55R E1A by immunoblot and indirect immunofluorescence. These studies indicate that 55R E1A is expressed late and is localized to the cytoplasm and to the nucleus. 55R E1A was able to activate the expression of viral genes in during infection, and could also promote productive replication of species C HAdV. 55R E1A was also found to interact with the S8 component of the proteasome component and knockdown of S8 was detrimental to viral replication dependent on 55R E1A.

MRI-Arthroscopy Correlation: The Knee

Instructional Course Lectures. 2012  |  Pubmed ID: 22301259

MRI findings can often be helpful in diagnosing and managing common knee injuries. The association between the normal and pathologic changes in the surgical anatomy of the knee commonly found on MRI and those found at arthroscopy can be demonstrated by examining a series of cases that correlate MRI and arthroscopy findings. Regular interactions are recommended between surgeons and musculoskeletal radiologists to improve MRI interpretation and achieve better surgical outcomes for patients.

Novel Clinical Trial Designs for the Development of New Antiretroviral Agents

AIDS (London, England). Feb, 2012  |  Pubmed ID: 22301412

The resounding success of combination antiretroviral efficacy for both treatment-naïve and -experienced patients - with 70% - 90% viral suppression rates in recent studies- has made registration trials for new agents challenging. With the inevitable specter of drug resistance, new agents must have a pathway to approval. The Forum for Collaborative HIV Research obtained input from concerned stakeholders including industry, clinical sciences, community advocacy and regulatory sciences (Food and Drug Administration and European Medicines Agency) to discuss how safety and efficacy of new agents could be demonstrated. Recognizing the shortfalls of superiority or non-inferiority trials in this environment, a new trial design for treatment-experienced patients, minimizing the risk for drug resistance but allowing full assessment of safety was proposed. The antiviral efficacy of an active investigational drug would be assessed by comparison to placebo as an add-on to a failing regimen in a short, 10-14 day study followed by institution of an optimized background regimen in both arms with investigational drug given to all patients. The follow-on stage would assess dose response, safety, durability of initial response and development of resistance. Additionally, a second safety trial could be conducted comparing patients randomized to the investigational agent plus a new OBR to those on a new OBR plus placebo. Finally, approval decisions could consider other long-term safety endpoints. Exposing treatment-naïve patients to investigational agents remains a controversial issue; stakeholders have different interpretations of risk-benefit for trials in this population which necessitate careful consideration before initiating trials in them.

The Impact of Depth of Infection and Postdischarge Surveillance on Rate of Surgical-site Infections in a Network of Community Hospitals

Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. Mar, 2012  |  Pubmed ID: 22314065

Objective. To describe the epidemiology of surgical-site infections (SSIs) in community hospitals and to explore the impact of depth of SSI, healthcare location at the time of diagnosis, and variations in surveillance practices on the overall rate of SSI. Design. Retrospective cohort study. Setting. Thirty-seven community hospitals in the southeastern United States. Patients. Consecutive sample of patients undergoing surgical procedures between July 1, 2007, and December 31, 2008. Methods. ANOVA was used to compare rates of SSIs, and the F test was used to compare the distribution of rates of SSIs. Wilcoxon rank-sum was used to test for differences in performance rankings of hospitals. Results. Following 177,706 surgical procedures, 1,919 SSIs were identified (incidence, 1.08 per 100 procedures). Sixty-four percent (1,223 of 1,919) of these were identified as complex SSIs; 87% of the complex SSIs were diagnosed in inpatient settings. The median proportion of superficial-incisional SSIs was 37% (interquartile range, 29.6%-49.5%). Postdischarge SSI surveillance was variable, with 58% of responding hospitals using surgeon letters. As reporting focus was narrowed from all SSIs to complex SSIs (incidence, 0.69 per 100 procedures) and, finally, to complex SSIs diagnosed in the inpatient setting (incidence, 0.51 per 100 procedures), variance in rates changed significantly ([Formula: see text]). Performance ranking of individual hospitals, based on rates of SSIs, differed significantly, depending on the reporting method utilized ([Formula: see text]). Conclusions. Inconsistent reporting methods focused on variable depths of infection and healthcare location at time of diagnosis significantly impact rates of SSI, distribution of rates of SSI, and hospital comparative-performance rankings. We believe that public reporting of SSI rates should be limited to complex SSIs diagnosed in the inpatient setting.

Prevalence of Healthcare-associated Infections in Acute Care Hospitals in Jacksonville, Florida

Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. Mar, 2012  |  Pubmed ID: 22314066

Objective. To determine healthcare-associated infection (HAI) prevalence in 9 hospitals in Jacksonville, Florida; to evaluate the performance of proxy indicators for HAIs; and to refine methodology in preparation for a multistate survey. Design. Point prevalence survey. Patients. Acute care inpatients of any age. Methods. HAIs were defined using National Healthcare Safety Network criteria. In each facility a trained primary team (PT) of infection prevention (IP) staff performed the survey on 1 day, reviewing records and collecting data on a random sample of inpatients. PTs assessed patients with one or more proxy indicators (abnormal white blood cell count, abnormal temperature, or antimicrobial therapy) for the presence of HAIs. An external IP expert team collected data from a subset of patient records reviewed by PTs to assess proxy indicator performance and PT data collection. Results. Of 851 patients surveyed by PTs, 51 had one or more HAIs (6.0%; 95% confidence interval, 4.5%-7.7%). Surgical site infections ([Formula: see text]), urinary tract infections ([Formula: see text]), pneumonia ([Formula: see text]), and bloodstream infections ([Formula: see text]) accounted for 75.8% of 58 HAIs detected by PTs. Staphylococcus aureus was the most common pathogen, causing 9 HAIs (15.5%). Antimicrobial therapy was the most sensitive proxy indicator, identifying 95.5% of patients with HAIs. Conclusions. HAI prevalence in this pilot was similar to that reported in the 1970s by the Centers for Disease Control and Prevention's Study on the Efficacy of Nosocomial Infection Control. Antimicrobial therapy was a sensitive screening variable with which to identify those patients at higher risk for infection and reduce data collection burden. Additional work is needed on validation and feasibility to extend this methodology to a national scale.

The Impact of Dementia Severity on Caregiver Burden in Frontotemporal Dementia and Alzheimer Disease

Alzheimer Disease and Associated Disorders. Feb, 2012  |  Pubmed ID: 22314247

Caregiver burden is greater in frontotemporal dementia (FTD) than in Alzheimer disease (AD). However, little is known of the impact of the 3 main clinical variants of FTD- behavioral-variant frontotemporal dementia (bvFTD), semantic dementia (SemDem), and progressive nonfluent aphasia (PNFA)-or the role of disease severity in caregiver burden. The Zarit Burden Inventory was used to measure caregiver burden of bvFTD (n=17), SemDem (n=20), PNFA (n=20), and AD (n=19) patients. Symptom duration, caregiver age, and relationship type were matched across groups. Moreover, a number of caregiver (mood, social network) and patient variables (functional disability, behavioral changes, relationship with caregiver, and dementia stage) were addressed to investigate their impact on caregiver burden. Caregivers of bvFTD patients reported the highest burden, whereas SemDem and PNFA caregivers reported burden similar to AD. A regression analysis revealed that caregiver burden in FTD, regardless of subtype, was explained by a model combining disease staging, relationship changes, and caregiver depression. Burden increased with disease severity in FTD. This study is the first to show that caregivers of SemDem, PNFA, and AD patients show similar burden, while confirming that bvFTD caregivers show higher burden than AD caregivers. More importantly, this study demonstrates that burden worsens with disease progression in FTD.

Inhibition of HMGB1 Enhances Bacterial Clearance and Protects Against P. Aeruginosa Pneumonia in Cystic Fibrosis

Molecular Medicine (Cambridge, Mass.). Feb, 2012  |  Pubmed ID: 22314397

Pulmonary infection with Pseudomonas (P.) aeruginosa and neutrophilic lung inflammation significantly contribute to morbidity and mortality in cystic fibrosis (CF). HMGB1, a ubiquitous DNA binding protein that promotes inflammatory tissue injury, is significantly elevated in CF sputum. However, its mechanistic and potential therapeutic implications in CF were previously unknown. We found that HMGB1 levels were significantly elevated in bronchoalveolar lavage fluids (BAL) of CF patients and CFTR(-/-) mice. Neutralizing anti-HMGB1 mAb conferred significant protection against P. aeruginosa-induced neutrophil recruitment, lung injury and bacterial infection in both CFTR(-/-) and wildtype mice. Alveolar macrophages isolated from mice treated with anti-HMGB1 mAb had improved phagocytic activity, which was suppressed by direct exposure to HMGB1. In addition, BAL from CF patients significantly impaired macrophage phagocytotic function and this impairment was attenuated by HMGB1-neutralizing antibodies. The HMGB1-mediated suppression of bacterial phagocytosis was attenuated in macrophages lacking toll-like receptor 4 (TLR4), suggesting a critical role for TLR4 in signaling HMGB1-mediated macrophage dysfunction. These studies demonstrate that the elevated levels of HMGB1 in CF airways are critical for neutrophil recruitment and persistent presence of P. aeruginosa in the lung. Thus, HMGB1 may provide a therapeutic target for reducing bacterial infection and lung inflammation in CF.

T2* Measurement of the Knee Articular Cartilage in Osteoarthritis at 3T

Journal of Magnetic Resonance Imaging : JMRI. Feb, 2012  |  Pubmed ID: 22314961

PURPOSE: To measure reproducibility, longitudinal and cross-sectional differences in T2* maps at 3 Tesla (T) in the articular cartilage of the knee in subjects with osteoarthritis (OA) and healthy matched controls. MATERIALS AND METHODS: MRI data and standing radiographs were acquired from 33 subjects with OA and 21 healthy controls matched for age and gender. Reproducibility was determined by two sessions in the same day, while longitudinal and cross-sectional group differences used visits at baseline, 3 and 6 months. Each visit contained symptomological assessments and an MRI session consisting of high resolution three-dimensional double-echo-steady-state (DESS) and co-registered T2* maps of the most diseased knee. A blinded reader delineated the articular cartilage on the DESS images and median T2* values were reported. RESULTS: T2* values showed an intra-visit reproducibility of 2.0% over the whole cartilage. No longitudinal effects were measured in either group over 6 months. T2* maps revealed a 5.8% longer T2* in the medial tibial cartilage and 7.6% and 6.5% shorter T2* in the patellar and lateral tibial cartilage, respectively, in OA subjects versus controls (P < 0.02). CONCLUSION: T2* mapping is a repeatable process that showed differences between the OA subject and control groups. J. Magn. Reson. Imaging 2012;. © 2012 Wiley Periodicals Inc.

Reliability and Clinical Significance of Mobility and Balance Assessments in Multiple Sclerosis

International Journal of Rehabilitation Research. Internationale Zeitschrift Für Rehabilitationsforschung. Revue Internationale De Recherches De Réadaptation. Mar, 2012  |  Pubmed ID: 22315143

The aim of the study was to establish the test-retest reliability, clinical significance and precision of four mobility and balance measures - the Timed 25-Foot Walk, Six-minute Walk, Timed Up and Go and the Berg Balance Scale - in individuals moderately affected by multiple sclerosis. Twenty four participants with multiple sclerosis (Extended Disability Status Score 5-6.5) were assessed on four measures of mobility and balance. The Timed 25-Foot Walk, Six-minute Walk and Timed Up and Go mobility outcome measures and the Berg Balance Scale were assessed by one assessor one week apart. Intraclass correlation coefficient (ICC) analysis was carried out to determine reliability. Minimal detectable change values were calculated to determine clinical significance; the standard error of each measurement was calculated to assess precision. All four outcome measures were found to be reliable: Timed 25-Foot Walk ICC=0.94, Six-minute Walk Test ICC=0.96, Timed Up and Go ICC=0.97 and Berg Balance Scale ICC=0.96. Minimal detectable change values were as follows: Timed 25-Foot Walk=12.6 s, Six-minute Walk Test=76.2 m, Timed Up and Go=10.6 s and Berg Balance Scale=7 points. Standard errors of measurement were as follows: Timed 25-Foot Walk=4.56 s, Six-minute Walk Test=27.48 m, Timed Up and Go=3.81 s and Berg Balance Scale=3 points. The test-retest reliability of these four outcome measures was found to be good. The calculated clinical significance and precision of these measures highlight the problems of assessing a heterogeneous clinical population.Die vorliegende Studie sollte die Test-Retest-Reliabilität, klinische Signifikanz und Präzision von vier Mobilitäts- und Gleichgewichtsübungen - Timed 25-Foot-Walk (T25FW), 6-Minuten-Gehtest, Timed-Up-and-Go-Test (TUG) und Berg-Balance-Skala - bei Personen mit mäßigen Beeinträchtigungen durch multiple Sklerose beurteilen. Dazu wurden 24 Teilnehmer mit multipler Sklerose (und einem Score von 5-6.5 auf der Expanded Disability Status-Skala (EDSS)) anhand von vier Mobilitäts- und Gleichgewichtsübungen beurteilt. Die ergebnisorientierten Mobilitäts-Messgrößen des Timed 25-Foot-Walk, des 6-Minuten-Gehtests und des Timed-Up-and-Go-Tests sowie die Berg-Balance-Skala wurden von einem Assessor im Abstand von jeweils einer Woche beurteilt. Anhand der Intraclass-Korrelationskoeffizientenanalyse (ICC) wurde die Reliabilität ermittelt. Minimal nachweisbare Änderungswerte wurden berechnet, um die klinische Signifikanz zu ermitteln; der Standardfehler jeder Messung wurde berechnet, um die Präzision zu ermitteln. Alle vier ergebnisorientierten Messgrößen erwiesen sich als zuverlässig: Der Timed 25-Foot-Walk-ICC=0.94, der 6-Minuten-Gehtest-ICC=0.96, der Timed-Up-and-Go-ICC=0.97 und der Berg-Balance-Skala-ICC=0.96. Die minimal nachweisbaren Änderungswerte lauteten: Timed 25-Foot-Walk=12.6 s, 6-Minuten-Gehtest=76.2 m, Timed-Up-and-Go=10.6 s und Berg-Balance-Skala=7 Punkte. Die Standard-Messfehler betrugen: Timed 25-Foot-Walk=4.56 s, 6-Minuten-Gehtest=27.48 m, Timed-Up-and-Go=3.81 s und Berg-Balance-Skala=3 Punkte. Die Test-Retest-Reliabilität dieser vier ergebnisorientierten Messgrößen erwies sich als gut. Die berechnete klinische Signifikanz und Präzision dieser Messgrößen zeigen die Problematik bei der Beurteilung einer heterogenen klinischen Population auf.El objetivo de este estudio fue establecer la fiabilidad test-retest, la significancia clínica y la precisión de estas cuatro mediciones de movilidad y equilibrio: la prueba cronometrada de la marcha de 25 pies (Timed 25-Foot Walk), la prueba de los seis minutos marcha (Six-minute Walk), la prueba cronometrada de levántate y anda (Timed Up and Go) y la Escala de equilibrio de Berg, en individuos afectados por esclerosis múltiple moderada. Se realizaron cuatro mediciones de movilidad y equilibrio a veinticuatro participantes con esclerosis múltiple (Escala extendida del estado de incapacidad 5-6.5). Los resultados de movilidad de las mediciones de la prueba cronometrada de la marcha de 25 pies, de la prueba de los seis minutos marcha y de la prueba cronometrada de levántate y anda, así como de la Escala de equilibrio de Berg, fueron analizados por un evaluador una semana más tarde. Se llevó a cabo el análisis del coeficiente de correlación intraclase (CCI) con el fin de determinar la fiabilidad. Los valores del cambio mínimo detectable se calcularon con el objetivo de establecer la significancia clínica; el error estándar de cada medición se calculó para evaluar la precisión. Se demostró la fiabilidad de los resultados de las cuatro mediciones: CCI de la prueba cronometrada de la marcha de 25 pies=0.94; CCI de la prueba de los seis minutos marcha=0.96; CCI de la prueba cronometrada de levántate y anda=0.97; CCI de la Escala de equilibrio de Berg=0.96. Los valores del cambio mínimo detectable fueron los siguientes: prueba cronometrada de la marcha de 25 pies=12.6 s; prueba de los seis minutos marcha=76.2 m; prueba cronometrada de levántate y anda=10.6 s; Escala de equilibrio de Berg=7 puntos. Los errores estándar de las mediciones fueron los siguientes: prueba cronometrada de la marcha de 25 pies=4.56 s; prueba de los seis minutos marcha=27.48 m; prueba cronometrada de levántate y anda=3.81 s; Escala de equilibrio de Berg=3 puntos. Se observó una buena fiabilidad test-retest de los resultados de estas cuatro mediciones. El cálculo de la significancia clínica y de la precisión de estas mediciones refleja la existencia de problemas a la hora de evaluar una población clínica heterogénea.Cette étude avait pour objet d'établir la répétabilité des tests, la signification clinique et la précision de quatre mesures de mobilité et d'équilibre - la marche chronométrée sur 7.6 m (« Timed 25-Foot Walk »), la marche de six minutes, la mesure « Timed Up and Go » et l'échelle d'équilibre de Berg - chez les personnes modérément affectées par la sclérose en plaques. Vingt quatre participants souffrant de la sclérose en plaques (score de statut d'invalidité prolongée de 5-6.5) ont été évalués pour quatre mesures de mobilité et d'équilibre. Les résultats des mesures de mobilité Timed 25-Foot Walk, marche de six minutes et Timed Up and Go et de l'échelle d'équilibre de Berg ont été évalués à une semaine d'intervalle. Une analyse du coefficient de corrélation intraclasse (CCI) a été effectuée pour déterminer la fiabilité des mesures. Les valeurs de changement détectable minimales ont été calculées afin de déterminer la signification clinique; l'erreur-type de chaque mesure a été calculée pour évaluer la précision. Les quatre mesures de résultats se sont avérées fiables: CCI marche T25FW=0.94, CCI test de marche de six minutes=0.96, CCI TUG=0.97 et CCI échelle d'équilibre de Berg=0.96. Les valeurs de changement détectable minimales étaient les suivantes: Marche T25FW=12.6 s, test de marche de six minutes=76.2 m, TUG=10.6 et échelle d'équilibre de Berg=7 points. Les erreurs types de mesure étaient les suivantes: Marche T25FW=4.56 s, test de marche de six minutes=27.48 m, TUG=3.81 et échelle d'équilibre de Berg=3 points. La répétabilité des tests de ces quatre résultats de mesures a été jugée satisfaisante. La signification clinique calculée et la précision de ces mesures mettent en évidence les problèmes d'évaluation d'une population clinique hétérogène.

MicroRNA-132 Dysregulation in Schizophrenia Has Implications for Both Neurodevelopment and Adult Brain Function

Proceedings of the National Academy of Sciences of the United States of America. Feb, 2012  |  Pubmed ID: 22315408

Schizophrenia is characterized by affective, cognitive, neuromorphological, and molecular abnormalities that may have a neurodevelopmental origin. MicroRNAs (miRNAs) are small noncoding RNA sequences critical to neurodevelopment and adult neuronal processes by coordinating the activity of multiple genes within biological networks. We examined the expression of 854 miRNAs in prefrontal cortical tissue from 100 control, schizophrenic, and bipolar subjects. The cyclic AMP-responsive element binding- and NMDA-regulated microRNA miR-132 was significantly down-regulated in both the schizophrenic discovery cohort and a second, independent set of schizophrenic subjects. Analysis of miR-132 target gene expression in schizophrenia gene-expression microarrays identified 26 genes up-regulated in schizophrenia subjects. Consistent with NMDA-mediated hypofunction observed in schizophrenic subjects, administration of an NMDA antagonist to adult mice results in miR-132 down-regulation in the prefrontal cortex. Furthermore, miR-132 expression in the murine prefrontal cortex exhibits significant developmental regulation and overlaps with critical neurodevelopmental processes during adolescence. Adult prefrontal expression of miR-132 can be down-regulated by pharmacologic inhibition of NMDA receptor signaling during a brief postnatal period. Several key genes, including DNMT3A, GATA2, and DPYSL3, are regulated by miR-132 and exhibited altered expression either during normal neurodevelopment or in tissue from adult schizophrenic subjects. Our data suggest miR-132 dysregulation and subsequent abnormal expression of miR-132 target genes contribute to the neurodevelopmental and neuromorphological pathologies present in schizophrenia.

A Peptide-Embedded Trifluoromethyl Ketone Catalyst for Enantioselective Epoxidation

Organic Letters. Feb, 2012  |  Pubmed ID: 22315978

The development of peptide-based oxidation catalysts that use a transiently generated dioxirane as the chemically active species is reported. The active catalyst is a chiral trifluoromethyl ketone (Tfk) with a pendant carboxylic acid that can be readily incorporated into a peptide. These peptides were capable of epoxidizing alkenes in high yield (up to 89%) and enantiomeric ratios (er) ranging from 69.0:31.0 to 91.0:9.0, depending on the alkene substitution pattern.

Effects of Growth Hormone Deficiency on Body Composition and Biomarkers of Cardiovascular Risk After Definitive Therapy for Acromegaly

Clinical Endocrinology. Feb, 2012  |  Pubmed ID: 22315983

BACKGROUND: Both growth hormone (GH) excess and GH deficiency are associated with body composition and biomarkers of cardiovascular risk in patients with pituitary disorders. However, the effects of developing GH deficiency after definitive treatment of acromegaly are largely unknown. OBJECTIVE: To determine whether development of GH deficiency after definitive therapy for acromegaly is associated with increased visceral adiposity and biomarkers of cardiovascular risk compared to GH sufficiency after definitive therapy for acromegaly. DESIGN: Cross-sectional PATIENTS: We studied three groups of subjects, all with a history of acromegaly (n=76): subjects with subsequent GH deficiency (GHD; n=31), subjects with subsequent GH sufficiency (GHS; n=25), and subjects with active acromegaly (AA; n=20). No study subjects were receiving somatostatin analogues, dopamine agonists or hGH. MEASUREMENTS: Body composition (by DXA), abdominal adipose tissue depots (by cross-sectional CT), total body water (by bioimpedance analysis) and carotid intima-media thickness (IMT) were measured. Fasting morning serum was collected for high-sensitivity C-reactive protein (hsCRP), lipids and lipoprotein levels. An oral glucose tolerance test was performed, and homeostasis model of assessment-insulin resistance (HOMA-IR) was calculated. RESULTS: Abdominal visceral adipose tissue, total adipose tissue, and total body fat were higher in subjects with GHD than GHS or AA (p < 0.05). Subcutaneous abdominal fat was higher, and fibrinogen and IMT were lower in GHD (but not GHS) than AA (p < 0.05). Patients with GHD had the highest hsCRP, followed by GHS, and hsCRP was lowest in AA (p < 0.05). Fasting glucose, 120-minute glucose, fasting insulin, HOMA-IR, and percent total body water were lower in GHD and GHS than AA (p < 0.05). Triglycerides were higher in GHS than AA (p < 0.05). Lean body mass, mean arterial pressure, total cholesterol, HDL, and LDL were comparable among groups. CONCLUSIONS: Development of GHD after definitive treatment of acromegaly may adversely affect body composition and inflammatory biomarkers of cardiovascular risk but does not appear to adversely affect glucose homeostasis, lipids and lipoproteins, or other cardiovascular risk markers. © 2012 Blackwell Publishing Ltd.

Initiating Breast Cancer by PIK3CA Mutation

Breast Cancer Research : BCR. Feb, 2012  |  Pubmed ID: 22315990

ABSTRACT: PIK3CA mutations confer constitutive activation of PI3K, which initiates intracellular kinase signaling cascades that promote cell proliferation and survival. Recent studies by Meyer and colleagues, and Liu and colleagues demonstrate that expression of the H1047R exon 20 mutant of PIK3CA in luminal mammary epithelial cells induces tumorigenesis, implying that PIK3CA mutation is an early event in breast cancer. PIK3CA-H1047R-initiated tumors exhibit variable dependence on the oncogene and variable sensitivity to PI3K inhibition. Amplification of the oncogenes MYC and MET was observed in tumors that recurred following silencing of PIK3CA-H1047R, suggesting that these pathways represent mechanisms of escape from PI3K inhibition.

Size and Support Effects for the Water-Gas Shift Catalysis over Gold Nanoparticles Supported on Model Al₂O₃ and TiO₂

Journal of the American Chemical Society. Feb, 2012  |  Pubmed ID: 22316316

The water-gas shift (WGS) reaction rate per total mole of Au under 7% CO, 8.5% CO₂, 22% H₂O, and 37% H₂ at 1 atm for Au/Al₂O₃ catalysts at 180°C and Au/TiO₂ catalysts at 120°C varies with the number average Au particle size (d) as d^-2.2±0.2 and d^-2.7±0.1 respectively. The use of non-porous and crystalline, model Al₂O₃ and TiO₂ supports allowed the imaging of the active catalyst and enabled a precise determination of the Au particle size distribution and particle shape using transmission electron microscopy (TEM). Further, the apparent reaction orders and the stretching frequency of CO adsorbed on Au⁰ (near 2100 cm^-1) determined by diffuse reflectance infrared spectroscopy (DRIFTS) depend on d. Due to the changes in reaction rates, kinetics and the CO stretching frequency with number average Au particle size, it is determined that the dominant active sites are the low coordinated corner Au sites, which are 3 and 7 times more active than the perimeter Au sites for Au/Al₂O₃ and Au/TiO₂ catalysts respectively and 10 times more active for Au on TiO₂ versus Al₂O₃. From operando Fourier transform infrared spectroscopy (FTIR) experiments, it is determined that the active Au sites are metallic in nature. In addition, Au/Al₂O₃ catalysts have a higher apparent H₂O order (0.63) and lower apparent activation energy (9 kJ mol^-1) than Au/TiO₂ catalysts with apparent H₂O order of -0.42 to -0.21 and activation energy of 45-60 kJ mol^-1 at near 120°C. From these data we conclude that the support directly participates by activating H₂O molecules.

An Approach to the Site-Selective Deoxygenation of Hydroxy Groups Based on Catalytic Phosphoramidite Transfer

Angewandte Chemie (International Ed. in English). Feb, 2012  |  Pubmed ID: 22319027

Selective: The deoxygenation of simple and complex natural products employing a readily synthesized phosphoramidite and tetrazole catalysts can be executed as a two-step process, without the need to isolate intermediate deoxygenation precursors. Furthermore, a peptide-based tetrazole catalyst controls the site selectivity of deoxyerythromycin synthesis, thus overcoming the notorious challenges with unprotected erythromycin A.

Ground Emergency Medical Services Requests for Helicopter Transfer of ST-segment Elevation Myocardial Infarction Patients Decrease Medical Contact to Balloon Times in Rural and Suburban Settings

Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. Feb, 2012  |  Pubmed ID: 22320366

ACADEMIC EMERGENCY MEDICINE 2012; 19:153-160 © 2012 by the Society for Academic Emergency Medicine ABSTRACT: Objectives:  ST-segment elevation myocardial infarction (STEMI) care is time-dependent. Many STEMI patients require interhospital helicopter transfer for percutaneous coronary intervention (PCI) if ground emergency medical services (EMS) initially transport the patient to a non-PCI center. This investigation models potential time savings of ground EMS requests for helicopter EMS (HEMS) transport of a STEMI patient directly to a PCI center, rather than usual transport to a local hospital with subsequent transfer. Methods:  Data from a multicenter retrospective chart review of STEMI patients transferred for primary PCI by a single HEMS agency over 12 months were used to model medical contact to balloon times (MCTB) for two scenarios: a direct-to-scene HEMS response and hospital rendezvous after ground EMS initiation of transfer. Results:  Actual MCTB median time for 36 hospital-initiated transfers was 160 minutes (range = 116 to 321 minutes). Scene response MCTB median time was estimated as 112 minutes (range = 69 to 187 minutes). The difference in medians was 48 minutes (95% confidence interval [CI] = 33 to 62 minutes). Hospital rendezvous MCTB median time was estimated as 113 minutes (range = 74 to 187 minutes). The difference in medians was 47 minutes (95% CI = 32 to 62 minutes). No patient had an actual MCTB time of less than 90 minutes; in the scene response and hospital rendezvous scenarios, 2 of 36 (6%) and 3 of 36 (8%), respectively, would have had MCTB times under 90 minutes. Conclusions:  In this setting, ground EMS initiation of HEMS transfers for STEMI patients has the potential to reduce MCTB time, but most patients will still not achieve MCTB time of less than 90 minutes.

Bioenergy Potential of the United States Constrained by Satellite Observations of Existing Productivity

Environmental Science & Technology. Feb, 2012  |  Pubmed ID: 22321165

United States (U.S.) energy policy includes an expectation that bioenergy will be a substantial future energy source. In particular, the Energy Independence and Security Act of 2007 (EISA) aims to increase annual U.S. biofuel (secondary bioenergy) production by more than three-fold, from 40 to 136 billion liters ethanol, which implies an even larger increase in biomass demand (primary energy), from roughly 2.9 to 7.4 EJ yr^-1. However, our understanding of many of the factors used to establish such energy targets is far from complete, introducing significant uncertainty into the feasibility of current estimates of bioenergy potential. Here, we utilized satellite-derived net primary productivity (NPP) data - measured for every 1 km² of the 7.2 million km² of vegetated land in the conterminous U.S. - to estimate primary bioenergy potential (PBP). Our results indicate that PBP of the conterminous U.S. ranges from roughly 5.9 to 22.1 EJ yr^-1, depending on land use. The low end of this range represents the potential when harvesting residues only, while the high end would require an annual biomass harvest over an area more than three times current U.S. agricultural extent. While EISA energy targets are theoretically achievable, we show that meeting these targets utilizing current technology would require either an 80% displacement of current crop harvest or the conversion of 60% of rangeland productivity. Accordingly, energy planning should include iteratively and realistically constrained bioenergy estimates for effective incorporation of bioenergy potential into the national energy portfolio.

Acute Kidney Injury After Placement of an Antibiotic-Impregnated Cement Spacer During Revision Total Knee Arthroplasty

The Journal of Arthroplasty. Feb, 2012  |  Pubmed ID: 22321301

We performed a retrospective cohort study of 84 patients to determine the incidence and predictors of acute kidney injury after antibiotic-impregnated cement spacer (ACS) placement for infected total knee arthroplasties. Acute kidney injury was defined as a more than 50% rise in serum creatinine from a preoperative baseline to a level greater than 1.4 mg/dL within 90 days postoperatively. Total incidence was 17% (n = 14; 95% confidence interval [CI], 10%-26%), and acute kidney injury was significantly associated with ACS tobramycin dose as both a dichotomous variable (>4.8 g; odds ratio, 5.87; 95% CI, 1.43-24.19; P = .01) and linear variable (odds ratio, 1.24 for every 1-g increase; 95% CI, 1.00-1.52; P = .049). Routine monitoring of serum creatinine and measurement of serum aminoglycoside levels in response to a threshold creatinine rise may be warranted after the placement of an aminoglycoside-containing ACS.

One-Year Efficacy and Safety Study of a 1.62% Testosterone Gel in Hypogonadal Men: Results of a 182-Day Open-Label Extension of a 6-Month Double-Blind Study

The Journal of Sexual Medicine. Feb, 2012  |  Pubmed ID: 22321357

Introduction.  A new formulation of testosterone gel (1.62% testosterone gel) with increased viscosity and reduced volume of application has been shown to be safe and efficacious after 182 days of use in a phase 3, double-blind study in adult hypogonadal males. Aim.  The objective of this study was to evaluate the efficacy and safety of the 1.62% testosterone gel after daily application to the skin in a 182-day (6-month) open-label extension of the initial 182-day double-blind study. Methods.  One hundred and sixty-three subjects, aged 26 to 77 years, continued on active (Continuing Active subjects) 1.62% testosterone gel for the remainder of the study (364 days total). In 28 subjects who had previously received placebo (Formerly Placebo subjects), the dose was titrated to normal levels of serum total testosterone (300-1,000 ng/dL). Dose adjustments for both groups were allowed at specific visits to maintain serum testosterone within a normal range. Main Outcome Measure.  The main outcome measure was the percentage of subjects with serum total testosterone average concentrations (C(av) ) within the normal range at day 364. Results.  On day 364, 77.9% (95% confidence interval: 70.0, 84.6) of the Continuing Active subjects and 87.0% (66.4, 97.2) of the Formerly Placebo subjects had C(av) values within the eugonadal range. The 1.62% testosterone gel was safe and well tolerated in this study. Conclusion.  Treatment with 1.62% testosterone gel for up to 1 year (182 days for the Formerly Placebo subjects, 364 days for the Continuing Active subjects) was safe and efficacious, resulting in >77% of treated subjects achieving normal serum testosterone levels at final visit. Kaufman JM, Miller MG, Fitzpatrick S, McWhirter C, and Brennan JJ. One-year efficacy and safety study of a 1.62% testosterone gel in hypogonadal men: Results of a 182-day open-label extension of a 6-month double-blind study. J Sex Med **;**:**-**.

Epidemiology and Management of Oesophageal Coin Impaction in Children

Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. Feb, 2012  |  Pubmed ID: 22321620

OBJECTIVE: The epidemiology of oesophageal coin impaction in children is poorly understood. We aimed to assess characteristics of patients with coin impaction and identify predictors of type of coin impacted and management strategies. METHODS: Cases of coin impaction from 2002 to 2009 were identified by querying a tertiary care centre's billing, clinical, and endoscopy databases for the International Classification of Diseases, 9th Revision code "935.1 - foreign body in the oesophagus." Charts were reviewed to confirm case status and to extract pertinent data. RESULTS: Of 113 patients with oesophageal coin impaction (55% male; 45% Caucasian; mean age 2.9 years), 65 (58%) swallowed a penny, 85 (80%) had the impaction in the proximal oesophagus, and 103 (91%) required a procedure. Thirty-five (34%) patients had an upper endoscopy performed by a gastroenterologist and 68 (66%) had a laryngoscopy or oesophagoscopy performed by an otolaryngologist. Only 2 minor complications were noted. There was no significant relationship between the coin type and location of impaction, but 99% of cases performed by otolaryngologists were for proximally impacted coins, compared to 49% for gastroenterologists (p<0.001). CONCLUSIONS: Oesophageal coin impaction disproportionately affected young children and extraction was frequently required. Whilst pennies were the most commonly impacted coin, there were no clear predictors on impaction based on coin type.

February Consultation #8

Journal of Cataract and Refractive Surgery. Feb, 2012  |  Pubmed ID: 22322176

Five-Factor Model Personality Disorder Prototypes: A Review of Their Development, Validity, and Comparison to Alternative Approaches

Journal of Personality. Feb, 2012  |  Pubmed ID: 22321333

In this manuscript the development of Five-Factor Model (FFM) personality disorder (PD) prototypes for the assessment of DSM-IV PDs are reviewed, as well as subsequent procedures for scoring individuals' FFM data with regard to these PD prototypes, including similarity scores and simple additive counts that are based on a quantitative prototype matching methodology. Both techniques, which result in very strongly correlated scores, demonstrate convergent and discriminant validity, and provide clinically useful information with regard to various forms of functioning. The techniques described here for use with FFM data are quite different from the prototype matching methods used elsewhere.

Insects on Plants: Explaining the Paradox of Low Diversity Within Specialist Herbivore Guilds

The American Naturalist. Mar, 2012  |  Pubmed ID: 22322223

Abstract Classical niche theory explains the coexistence of species through their exploitation of different resources. Assemblages of herbivores coexisting on a particular plant species are thus expected to be dominated by species from host-specific guilds with narrow, coexistence-facilitating niches rather than by species from generalist guilds. Exactly the opposite pattern is observed for folivores feeding on trees in New Guinea. The least specialized mobile chewers were the most species rich, followed by the moderately specialized semiconcealed and exposed chewers. The highly specialized miners and mesophyll suckers were the least species-rich guilds. The Poisson distribution of herbivore species richness among plant species in specialized guilds and the absence of a negative correlation between species richness in different guilds on the same plant species suggest that these guilds are not saturated with species. We show that herbivore assemblages are enriched with generalists because these are more completely sampled from regional species pools. Herbivore diversity increases as a power function of plant diversity, and the rate of increase is inversely related to host specificity. The relative species diversity among guilds is thus scale dependent, as the importance of specialized guilds increases with plant diversity. Specialized insect guilds may therefore comprise a larger component of overall diversity in the tropics (where they are also poorly known taxonomically) than in the temperate zone, which has lower plant diversity.

Dorsal Root Ganglia Damage in SIV-Infected Rhesus Macaques An Animal Model of HIV-Induced Sensory Neuropathy

The American Journal of Pathology. Feb, 2012  |  Pubmed ID: 22322298

HIV-associated sensory neuropathy (HIV-SN) is currently the most common neurological complication of chronic HIV infection and continues to substantially affect patient quality of life. Mechanisms underlying the neuronal damage and loss observed in sensory ganglia of HIV-infected individuals have not been sufficiently studied. The present study aimed to develop and characterize a model of HIV-SN using SIV-infected CD8 T-cell-depleted rhesus macaques (Macaca mulatta). Uninfected controls (n = 5), SIV-infected CD8-depleted (n = 4), and SIV-infected non-CD8-depleted (n = 6) animals were used. Of the six non-CD8-depleted animals, three were conventional progressors (progressing to AIDS >1 year after infection) and three were rapid progressors (AIDS within 6 months). Dorsal root ganglia (DRG) were examined for histological hallmarks of HIV-SN, including satellitosis, presence of Nageotte nodules, and neuronophagia, as well as increased numbers of CD68(+) macrophages and abundant viral replication. In contrast to non-CD8-depleted animals, which had mild to moderate DRG pathology, the CD8-depleted SIV-infected animals had moderate to severe DRG damage, with increased numbers of CD68(+) satellite cells. Additionally, there was marked active viral replication in the affected DRG. These findings confirm that many features of HIV-SN can be recapitulated in the CD8-depleted SIV-infected rhesus macaque model within a short time frame and illustrate the importance of this model for study of sensory neuropathy.

HANDS ON: How to Perform VT Ablation with a Percutaneous Left Ventricular Assist Device

Heart Rhythm : the Official Journal of the Heart Rhythm Society. Feb, 2012  |  Pubmed ID: 22322326

Improving Direct-Care Compensation in Nursing Homes: Medicaid Wage Pass-through Adoption, 1999 - 2004

Journal of Health Politics, Policy and Law. Feb, 2012  |  Pubmed ID: 22323236

Because states play such a prominent role in the U.S. health care system, they have long grappled with how to best control health care costs while maintaining high quality of care. There are many policy tools available to address efficiency and quality concerns - from pure state regulation to market-oriented competition designs. Given public discourse and official party platforms, one would assume that states controlled by Democrats would be more likely to adopt regulatory reforms. This study examines whether party control, as well as other economic and political factors, is associated with adopting wage pass-through (WPT) policies, which direct a portion of Medicaid reimbursement or its increase toward nursing home staff in an effort to reduce staff turnover, thereby increasing efficiency and the quality of care provided. Contrary to expectations, results indicate that states with Republican governors were against WPT adoption only when for-profit industry pressure increased; otherwise, they were more likely to favor adoption than their Democratic counterparts. This suggests a more complex relationship between partisanship and state-level policy adoption than is typically assumed. Results also indicate that state officials reacted predictably to prevailing political and economic conditions affecting state fiscal-year decisions but required sufficient governing capacity to successfully integrate WPTs into existing reimbursement system arrangements. This suggests that WPTs represent a hybrid between comprehensive and incremental policy change.

Pharmacological Interventions for Geriatric Cachexia: a Narrative Review of the Literature

The Journal of Nutrition, Health & Aging. 2012  |  Pubmed ID: 22323350

Objective: The objective of this review was to investigate the range of pharmacological interventions that have been studied for treatment of geriatric cachexia, and to evaluate their effect on selected clinical outcomes in this population. Methods: Databases including Medline and Cochrane Central Register of Controlled Trials were searched up to March 2010 with search terms including "cache*", "intervention", "megestrol acetate" and "cytokine inhibitors". Studies investigating subjects with mean age <60y or disease-related cachexia were excluded. Outcomes assessed were weight or BMI, body composition, appetite and laboratory parameters indicative of cachexia. Results: Fifteen publications met the selection criteria, reporting on ten studies. Seven studies investigated use of megestrol acetate (MA): two randomised controlled trials, one case control study, two pre-test/post-test studies and two retrospective chart reviews. Weight/BMI was common amongst outcomes and these studies showed an improvement in weight compared with baseline. MA studies which investigated body composition, appetite and/or laboratory parameters provided some evidence for improvement in these outcomes. Three randomised controlled trials investigated the use of other interventions: ghrelin, growth hormone and vitamin supplementations. All demonstrated a significant increase in lean body mass. The only other outcome of interest in these three trials was weight in one study with a significant increase demonstrated. Conclusion: Little investigation has been conducted in this population and the diagnosis of cachexia is problematic however these trials provide preliminary evidence for beneficial outcomes in older adults likely to have cachexia. Further high quality adequately powered prospective studies are necessary to provide effective treatment for geriatric cachexia.

Basal Growth Hormone Concentration Increased Following a Weight Loss Focused Dietary Intervention in Older Overweight and Obese Women

The Journal of Nutrition, Health & Aging. 2012  |  Pubmed ID: 22323353

Objectives: Growth and sex steroid hormones decrease with aging and obesity. The effect of dietary weight loss and exercise training lifestyle interventions was examined on hormones as well as determining their relationships with physical function in older obese and overweight adults. Design: Individuals were randomized into one of four 18 month interventions: Healthy Lifestyle (HL), Exercise, Diet, and Exercise-Diet. Setting: Clinical research setting with facility based exercise and nutrition education and behavior classrooms. Participants: Older (≥60 yrs) overweight and obese (BMI≥28 kg/m2) adults with knee osteoarthritis (n=309) were recruited for the study. Intervention: Weight loss goal for Diet groups was ≥5%. Exercise groups trained (mostly walking and resistance training) 3 days/week for 60 min/session. Measurements: Body weight, growth hormone (GH), corticosterone, sex-hormone binding globulin (SHBG), testosterone, and dehydroepiandrosterone (DHEA) were measured at baseline, 6, and 18 months. Physical function was determined through performance task (6-min walking distance) and self-reported questionnaires (Western Ontario McMaster University Osteoarthritis Index-WOMAC) at similar time points. Results: Diet, Exercise, and Exercise-Diet groups lost 4.9%, 3.5%, and 6.2% of their weight at 18 months, respectively. There was a significant diet treatment effect on GH levels in women as higher concentrations of this hormone were apparent following dietary weight loss intervention (p=0.01). No other hormones were affected by either diet or exercise treatments in men or women. A significant inverse correlation between baseline 6-minute walking distance and SHBG (r=-0.33) was found in men. Conclusion: The increase in basal GH levels from the diet treatment in women suggests that this lifestyle behavior intervention may mitigate the age- and obesity-related decreases in growth hormone levels, to help preserve muscle mass, strength, and physical function in older adults.

F Box Protein FBXL2 Targets Cyclin D2 for Ubiquitination and Degradation to Inhibit Leukemic Cell Proliferation

Blood. Feb, 2012  |  Pubmed ID: 22323446

Hematologic maligancies exhibit a growth advantage by upregulation of components within the molecular apparatus involved in cell cycle progression. The SCF (Skip-Cullin1-F-box protein) E3 ligase family provides homeostatic feedback control of cell division by mediating ubiquitination and degradation of cell cycle proteins. By screening of several previously undescribed E3 ligase components, we describe the behavior of a relatively new SCF subunit, termed FBXL2, that ubiquitinates and destabilizes cyclin D2 protein leading to G0 phase arrest and apoptosis in leukemic and B lymphoblastoid cell lines. FBXL2 expression was strongly suppressed, and yet cyclin D2 protein levels were robustly expressed in AML and ALL patient samples. Depletion of endogenous FBXL2 stabilized cyclin D2 levels whereas ectopically expressed FBXL2 decreased cyclin D2 lifespan. FBXL2 did not bind a phosphodegron within its substrate typical of other F box proteins, but uniquely targeted a calmodulin-binding signature within cyclin D2 to facilitate its polyubiquitination. Calmodulin competes with the F box protein for access to this motif where it bound and protected cyclin D2 from FBXL2. Calmodulin reversed FBXL2-induced G0 phase arrest and attenuated FBXL2-induced apoptosis of lymphoblastoid cells. These results suggest an anti-proliferative effect of SCF(FBXL2) in lymphoproliferative malignancies.

Tim-3 is an Inducible Human Natural Killer Cell Receptor That Enhances Interferon Gamma Production in Response to Galectin-9

Blood. Feb, 2012  |  Pubmed ID: 22323453

Natural killer (NK) cell function is regulated by the integration of signals received from activating and inhibitory receptors. Here we show that a novel immune receptor, Tim-3, is expressed on resting human NK cells and is upregulated upon activation. The NK92 NK cell line engineered to overexpress Tim-3 showed a marked increase in IFN-γ production in the presence of soluble rhGal-9 or Raji tumor cells engineered to express Gal-9. The Tim-3(+) population of low dose IL-12/IL-18-activated primary NK cells significantly increased IFN-γ production in response to soluble rhGal-9, Gal-9 presented by cell lines, and primary acute myelogenous leukemia (AML) targets that endogenously express Gal-9. This effect is highly specific as Tim-3 antibody blockade significantly decreased IFN-γ production and Tim-3 crosslinking induced ERK activation and degradation of IκBα. Exposure to Gal-9 expressing target cells had little effect on CD107a degranulation. Reconstituted NK cells obtained from patients after hematopoietic cell transplant had diminished expression of Tim-3 compared to paired donors. This observation correlates with the known IFN-γ defect seen early post-transplant. In conclusion, we show that Tim-3 functions as a human NK cell co-receptor to enhance IFN-γ production, which has important implications for control of infectious disease and cancer.

Female Reproductive Tract Form Drives the Evolution of Complex Sperm Morphology

Proceedings of the National Academy of Sciences of the United States of America. Feb, 2012  |  Pubmed ID: 22323584

The coevolution of female mate preferences and exaggerated male traits is a fundamental prediction of many sexual selection models, but has largely defied testing due to the challenges of quantifying the sensory and cognitive bases of female preferences. We overcome this difficulty by focusing on postcopulatory sexual selection, where readily quantifiable female reproductive tract structures are capable of biasing paternity in favor of preferred sperm morphologies and thus represent a proximate mechanism of female mate choice when ejaculates from multiple males overlap within the tract. Here, we use phylogenetically controlled generalized least squares and logistic regression to test whether the evolution of female reproductive tract design might have driven the evolution of complex, multivariate sperm form in a family of aquatic beetles. The results indicate that female reproductive tracts have undergone extensive diversification in diving beetles, with remodeling of size and shape of several organs and structures being significantly associated with changes in sperm size, head shape, gains/losses of conjugation and conjugate size. Further, results of Bayesian analyses suggest that the loss of sperm conjugation is driven by elongation of the female reproductive tract. Behavioral and ultrastructural examination of sperm conjugates stored in the female tract indicates that conjugates anchor in optimal positions for fertilization. The results underscore the importance of postcopulatory sexual selection as an agent of diversification.

Impact of Cross-protective Vaccines on Epidemiological and Evolutionary Dynamics of Influenza

Proceedings of the National Academy of Sciences of the United States of America. Feb, 2012  |  Pubmed ID: 22323589

Large-scale immunization has profoundly impacted control of many infectious diseases such as measles and smallpox because of the ability of vaccination campaigns to maintain long-term herd immunity and, hence, indirect protection of the unvaccinated. In the case of human influenza, such potential benefits of mass vaccination have so far proved elusive. The central difficulty is a considerable viral capacity for immune escape; new pandemic variants, as well as viral escape mutants in seasonal influenza, compromise the buildup of herd immunity from natural infection or deployment of current vaccines. Consequently, most current influenza vaccination programs focus mainly on protection of specific risk groups, rather than mass prophylactic protection. Here, we use epidemiological models to show that emerging vaccine technologies, aimed at broad-spectrum protection, could qualitatively alter this picture. We demonstrate that sustained immunization with such vaccines could-through potentially lowering transmission rates and improving herd immunity-significantly moderate both influenza pandemic and seasonal epidemics. More subtly, phylodynamic models indicate that widespread cross-protective immunization could slow the antigenic evolution of seasonal influenza; these effects have profound implications for a transition to mass vaccination strategies against human influenza, and for the management of antigenically variable viruses in general.

Temporally-independent Functional Modes of Spontaneous Brain Activity

Proceedings of the National Academy of Sciences of the United States of America. Feb, 2012  |  Pubmed ID: 22323591

Resting-state functional magnetic resonance imaging has become a powerful tool for the study of functional networks in the brain. Even "at rest," the brain's different functional networks spontaneously fluctuate in their activity level; each network's spatial extent can therefore be mapped by finding temporal correlations between its different subregions. Current correlation-based approaches measure the average functional connectivity between regions, but this average is less meaningful for regions that are part of multiple networks; one ideally wants a network model that explicitly allows overlap, for example, allowing a region's activity pattern to reflect one network's activity some of the time, and another network's activity at other times. However, even those approaches that do allow overlap have often maximized mutual spatial independence, which may be suboptimal if distinct networks have significant overlap. In this work, we identify functionally distinct networks by virtue of their temporal independence, taking advantage of the additional temporal richness available via improvements in functional magnetic resonance imaging sampling rate. We identify multiple "temporal functional modes," including several that subdivide the default-mode network (and the regions anticorrelated with it) into several functionally distinct, spatially overlapping, networks, each with its own pattern of correlations and anticorrelations. These functionally distinct modes of spontaneous brain activity are, in general, quite different from resting-state networks previously reported, and may have greater biological interpretability.

A Randomized Trial of Varenicline (Chantix) for the Treatment of Spinocerebellar Ataxia Type 3

Neurology. Feb, 2012  |  Pubmed ID: 22323747

OBJECTIVE:The objective of this double-blind, placebo-controlled, randomized study was to evaluate the efficacy of varenicline (Chantix), a partial agonist at α4β2 neuronal nicotinic acetylcholine receptors used for smoking cessation, in patients with spinocerebellar ataxia (SCA) 3. METHODS:Patients with genetically confirmed SCA3 were randomly assigned to receive either varenicline (4 weeks for titration and 4 weeks at a dose of 1 mg twice daily) or placebo. Outcome measures included changes in the Scale for the Rating and Assessment of Ataxia (SARA) scores at endpoint (8 weeks) compared with baseline, a timed 25-foot walk and 9-hole peg test, measurements of mood and anxiety, and adverse events. RESULTS:Twenty patients with SCA3 (mean age = 51 ± 10.98 years; mean disease duration = 14 ± 9.82 years; mean SARA score = 16.13 ± 4.67) were enrolled in the study, and data on 18 patients were analyzed in period I. The most common side effect associated with varenicline was nausea. Improvements were noted in the SARA subsections for gait (p = 0.04), stance (p = 0.03), rapid alternating movements (p = 0.003), and timed 25-foot walk (p = 0.05) and Beck Depression Inventory scores (p = 0.03) in patients taking varenicline compared with those taking placebo at endpoint, with a trend toward improvement in the SARA total score (p = 0.06) in the varenicline group. CONCLUSIONS:In this controlled study, varenicline significantly improved axial symptoms and rapid alternating movements in patients with SCA3 as measured by SARA subscores and was fairly well tolerated.Classification of evidence:This study provides Class II evidence that varenicline improved the axial functions of gait, stance, and timed 25-foot walk but did not improve appendicular function, except for rapid alternating movements, in adult patients with genetically confirmed SCA3.

Cesarean Hysterectomy Requiring Emergent Thoracotomy: a Case Report of a Complication of Placenta Percreta Requiring a Multidisciplinary Effort

The Journal of Reproductive Medicine. Jan-Feb, 2012  |  Pubmed ID: 22324270

Currently a leading indication for cesarean hysterectomy among multiparous women, placenta accreta is associated with significant maternal morbidity and mortality.

Does Glycemic Variability Impact Mood and Quality of Life?

Diabetes Technology & Therapeutics. Feb, 2012  |  Pubmed ID: 22324383

Abstract Background: Diabetes is a chronic condition that significantly impacts quality of life. Poor glycemic control is associated with more diabetes complications, depression, and worse quality of life. The impact of glycemic variability on mood and quality of life has not been studied. Methods: A descriptive exploratory design was used. Twenty-three women with type 2 diabetes wore a continuous glucose monitoring system for 72 h and completed a series of questionnaires. Measurements included (1) glycemic control shown by glycated hemoglobin and 24-h mean glucose, (2) glycemic variability shown by 24-h SD of the glucose readings, continuous overall net glycemic action (CONGA), and Fourier statistical models to generate smoothed curves to assess rate of change defined as "energy," and (3) mood (depression, anxiety, anger) and quality of life by questionnaires. Results: Women with diabetes and co-morbid depression had higher anxiety, more anger, and lower quality of life than those without depression. Certain glycemic variability measures were associated with mood and quality of life. The 24-h SD of the glucose readings and the CONGA measures were significantly associated with health-related quality of life after adjusting for age and weight. Fourier models indicated that certain energy components were significantly associated with depression, trait anxiety, and overall quality of life. Finally, subjects with higher trait anxiety tended to have steeper glucose excursions. Conclusions: Data suggest that greater glycemic variability may be associated with lower quality of life and negative moods. Implications include replication of the study in a larger sample for the assessment of blood glucose fluctuations as they impact mood and quality of life.

Improvement of Neurological Recovery and Stimulation of Neural Progenitor Cell Proliferation by Intrathecal Administration of Sonic Hedgehog

Journal of Neurosurgery. Feb, 2012  |  Pubmed ID: 22324418

Object Sonic hedgehog (Shh) is a glycoprotein molecule that has been shown to be associated with the proliferative capacity of endogenous neural precursor cells during embryonic development. It has also been shown to regulate the proliferative capacity of neural stem cells in the adult subventricular zone (SVZ), which are also upregulated in animal models of ischemic stroke. In the present study, the effects of exogenous administration of intrathecal Shh protein were examined in the setting of a rodent model of ischemic stroke, with particular attention given to endogenous neural stem cell proliferation and migration as well as inducible differences in behavioral recovery. Methods A rodent model of ischemic stroke was created using the intraluminal suture method of reversible middle cerebral artery occlusion. Animals were treated with intrathecal administration of Shh protein at 24 hours after the onset of the stroke. Behavioral testing was performed, and the animals were killed for measurements of infarct volume 7 days after stroke. Immunohistochemical staining was performed and measurements of cellular proliferation were obtained, with a focus on the proportion and distribution of neural progenitor cells in the SVZ. These values were compared across experimental groups. Results Treatment with intrathecal Shh protein resulted in significant improvement in behavioral function compared with the control group, with a significant reduction of ischemic tissue in the cerebral hemisphere. An increase of nestin immunoreactive cells was observed along the SVZ. Conclusions Intrathecal Shh agonist at doses that upregulate spinal cord GLI1 transcription increases the population of neural precursor cells after spinal cord injury in adult rats. Intrathecal administration of Shh protein appears to have a neuroprotective effect in animal models of ischemic stroke and is associated with improved behavioral recovery, which may be related to its effects on neurogenesis in the SVZ and could be associated with improved functional recovery.

Reversed Umbilical Arterial End Diastolic Flow, Sildenafil Treatment and Early Stillbirths

BJOG : an International Journal of Obstetrics and Gynaecology. Mar, 2012  |  Pubmed ID: 22324929

Non-hispanic Whites Have Higher Risk for Pulmonary Impairment from Pulmonary Tuberculosis

BMC Public Health. Feb, 2012  |  Pubmed ID: 22325005

ABSTRACT: BACKGROUND: Disparities in outcomes associated with race and ethnicity are well documented for many diseases and patient populations. Tuberculosis (TB) disproportionately affects economically disadvantaged, racial and ethnic minority populations. Pulmonary impairment after tuberculosis (PIAT) contributes heavily to the societal burden of TB. Individual impacts associated with PIAT may vary by race/ethnicity or socioeconomic status. METHODS: We analyzed the pulmonary function of 320 prospectively identified patients with pulmonary tuberculosis who had completed at least 20 weeks standard anti-TB regimes by directly observed therapy. We compared frequency and severity of spirometry-defined PIAT in groups stratified by demographics, pulmonary risk factors, and race/ethnicity, and examined clinical correlates to pulmonary function deficits. RESULTS: Pulmonary impairment after tuberculosis was identified in 71% of non-Hispanic Whites, 58% of non-Hispanic Blacks, 49% of Asians and 32% of Hispanics (p < 0.001). Predictors for PIAT varied between race/ethnicity. PIAT was evenly distributed across all levels of socioeconomic status suggesting that PIAT and socioeconomic status are not related. PIAT and its severity were significantly associated with abnormal chest x-ray, p < 0.0001. There was no association between race/ethnicity and time to beginning TB treatment, p = 0.978. CONCLUSIONS: Despite controlling for cigarette smoking, socioeconomic status and time to beginning TB treatment, non-Hispanic White race/ethnicity remained an independent predictor for disproportionately frequent and severe pulmonary impairment after tuberculosis relative to other race/ethnic groups. Since race /ethnicity was self reported and that race is not a biological construct: these findings must be interpreted with caution. However, because race/ ethnicity is a proxy for several other unmeasured host, pathogen or environment factors that may contribute to disparate health outcomes, these results are meant to suggest hypotheses for further research.

Family Matters: Sexual Dimorphism in Cardiovascular Disease

Lancet. Feb, 2012  |  Pubmed ID: 22325188

Molecular Microcircuitry Underlies Functional Specification in a Basal Ganglia Circuit Dedicated to Vocal Learning

Neuron. Feb, 2012  |  Pubmed ID: 22325205

Similarities between speech and birdsong make songbirds advantageous for investigating the neurogenetics of learned vocal communication-a complex phenotype probably supported by ensembles of interacting genes in cortico-basal ganglia pathways of both species. To date, only FoxP2 has been identified as critical to both speech and birdsong. We performed weighted gene coexpression network analysis on microarray data from singing zebra finches to discover gene ensembles regulated during vocal behavior. We found ∼2,000 singing-regulated genes comprising three coexpression groups unique to area X, the basal ganglia subregion dedicated to learned vocalizations. These contained known targets of human FOXP2 and potential avian targets. We validated biological pathways not previously implicated in vocalization. Higher-order gene coexpression patterns, rather than expression levels, molecularly distinguish area X from the ventral striato-pallidum during singing. The previously unknown structure of singing-driven networks enables prioritization of molecular interactors that probably bear on human motor disorders, especially those affecting speech.

Bayesian Functional Integral Method for Inferring Continuous Data from Discrete Measurements

Biophysical Journal. Feb, 2012  |  Pubmed ID: 22325261

Inference of the insulin secretion rate (ISR) from C-peptide measurements as a quantification of pancreatic β-cell function is clinically important in diseases related to reduced insulin sensitivity and insulin action. ISR derived from C-peptide concentration is an example of nonparametric Bayesian model selection where a proposed ISR time-course is considered to be a "model". An inferred value of inaccessible continuous variables from discrete observable data is often problematic in biology and medicine, because it is a priori unclear how robust the inference is to the deletion of data points, and a closely related question, how much smoothness or continuity the data actually support. Predictions weighted by the posterior distribution can be cast as functional integrals as used in statistical field theory. Functional integrals are generally difficult to evaluate, especially for nonanalytic constraints such as positivity of the estimated parameters. We propose a computationally tractable method that uses the exact solution of an associated likelihood function as a prior probability distribution for a Markov-chain Monte Carlo evaluation of the posterior for the full model. As a concrete application of our method, we calculate the ISR from actual clinical C-peptide measurements in human subjects with varying degrees of insulin sensitivity. Our method demonstrates the feasibility of functional integral Bayesian model selection as a practical method for such data-driven inference, allowing the data to determine the smoothing timescale and the width of the prior probability distribution on the space of models. In particular, our model comparison method determines the discrete time-step for interpolation of the unobservable continuous variable that is supported by the data. Attempts to go to finer discrete time-steps lead to less likely models.

Antiviral Effect of HPMPC (Cidofovir®), Entrapped in Cationic Liposomes: In Vitro Study on MDBK Cell and BHV-1 Virus

Journal of Controlled Release : Official Journal of the Controlled Release Society. Feb, 2012  |  Pubmed ID: 22326403

We designed and synthesised a series of new cationic lipids based on spermine linked to various hydrophobic anchors. These lipids could be potentially useful for the preparation of stable cationic liposomes intended for the construction of drug targeting systems applicable in the field of anticancer/antiviral therapy, vaccine carriers, and vectors for the gene therapy. Low in vitro toxicity was found for these compounds, especially for LD1, in several cell lines. The delivery of both a fluorescence marker (calcein) and antiviral drugs into cells has been achieved owing to a large extent of internalization of cationic liposomes (labelled by Lyssamine-Rhodamine PE or fluorescein-PE) as demonstrated by fluorescent microscopy and quantified by flow cytometry. The bovine herpes virus type 1 (BHV-1) virus infection in vitro model using MDBK cells was employed to study the effect of the established antiviral drug HPMPC (Cidofovir®) developed by Prof. A. Holý. Inhibition of BHV-1 virus replication was studied by quantitative RT-PCR and confirmed by both Hoffman modulation contrast microscopy and transmission electron microscopy. We found that in vitro antiviral activity of HPMPC was significantly improved by formulation in cationic liposomes, which decreased the viral replication by about 2 orders of magnitude.

The Genome of the Xerotolerant Mold Wallemia Sebi Reveals Adaptations to Osmotic Stress and Suggests Cryptic Sexual Reproduction

Fungal Genetics and Biology : FG & B. Feb, 2012  |  Pubmed ID: 22326418

Wallemia (Wallemiales, Wallemiomycetes) is a genus of xerophilic Fungi of uncertain phylogenetic position within Basidiomycota. Most commonly found as food contaminants, species of Wallemia have also been isolated from hypersaline environments. The ability to tolerate environments with reduced water activity is rare in Basidiomycota. We sequenced the genome of W. sebi in order to understand its adaptations for surviving in osmotically challenging environments, and we performed phylogenomic and ultrastructural analyses to address its systematic placement and reproductive biology. W. sebi has a compact genome (9.8Mb), with few repeats and the largest fraction of genes with functional domains compared with other Basidiomycota. We applied several approaches to searching for osmotic stress-related proteins. In silico analyses identified 93 putative osmotic stress proteins; homology searches showed the HOG (High Osmolarity Glycerol) pathway to be mostly conserved. Despite the seemingly reduced genome, several gene family expansions and a high number of transporters (549) were found that also provide clues to the ability of W. sebi to colonize harsh environments. Phylogenetic analyses of a 71-protein dataset support the position of Wallemia as the earliest diverging lineage of Agaricomycotina, which is confirmed by septal pore ultrastructure that shows the septal pore apparatus as a variant of the Tremella-type. Mating type gene homologs were identified although we found no evidence of meiosis during conidiogenesis, suggesting there may be aspects of the life cycle of W. sebi that remain cryptic.

Chemical Genetic Profiling of the Microtubule-targeting Agent Peloruside A in Budding Yeast Saccharomyces Cerevisiae

Gene. Feb, 2012  |  Pubmed ID: 22326528

Peloruside A, a microtubule-stabilising agent from a New Zealand marine sponge, inhibits mammalian cell division by a similar mechanism to that of the anticancer drug paclitaxel. Wild type budding yeast Saccharomyces cerevisiae (haploid strain BY4741) showed growth sensitivity to peloruside A with an IC(50) of 35μM. Sensitivity was increased in a mad2Δ (Mitotic Arrest Deficient 2) deletion mutant (IC(50)=19μM). Mad2 is a component of the spindle-assembly checkpoint complex that delays the onset of anaphase in cells with defects in mitotic spindle assembly. Haploid mad2Δ cells were much less sensitive to paclitaxel than to peloruside A, possibly because the peloruside binding site on yeast tubulin is more similar to mammalian tubulin than the taxoid site where paclitaxel binds. In order to obtain information on the primary and secondary targets of peloruside A in yeast, a microarray analysis of yeast heterozygous and homozygous deletion mutant sets was carried out. Haploinsufficiency profiling (HIP) failed to provide hits that could be validated, but homozygous profiling (HOP) generated twelve validated genes that interact with peloruside A in cells. Five of these were particularly significant: RTS1, SAC1, MAD1, MAD2, and LSM1. In addition to its known target tubulin, based on these microarray 'hits', peloruside A was seen to interact genetically with other cell proteins involved in the cell cycle, mitosis, RNA splicing, and membrane trafficking.

Comp Plan: A Computer Program to Generate Dose and Radiobiological Metrics from Dose-volume Histogram Files

Medical Dosimetry : Official Journal of the American Association of Medical Dosimetrists. Feb, 2012  |  Pubmed ID: 22326733

Treatment planning studies often require the calculation of a large number of dose and radiobiological metrics. To streamline these calculations, a computer program called Comp Plan was developed using MATLAB. Comp Plan calculates common metrics, including equivalent uniform dose, tumor control probability, and normal tissue complication probability from dose-volume histogram data. The dose and radiobiological metrics can be calculated for the original data or for an adjusted fraction size using the linear quadratic model. A homogeneous boost dose can be added to a given structure if desired. The final output is written to an Excel file in a format convenient for further statistical analysis. Comp Plan was verified by independent calculations. A lung treatment planning study comparing 45 plans for 7 structures using up to 6 metrics for each structure was successfully analyzed within approximately 5 minutes with Comp Plan. The code is freely available from the authors on request.

Reactivated Memories Compete for Expression After Pavlovian Extinction

Behavioural Processes. Feb, 2012  |  Pubmed ID: 22326812

We view the response decrement resulting from extinction treatment as an interference effect, in which the reactivated memory from acquisition competes with the reactivated memory from extinction for behavioral expression. For each of these memories, reactivation is proportional to both the strength of the stimulus-outcome association and the quality of the facilitatory cues for that association which are present at test. Here we review basic extinction and recovery-from-extinction phenomena, showing how these effects are explicable in this associative interference framework. Moreover, this orientation has and continues to dictate efficient manipulations for minimizing recovery from extinction. This in turn suggests procedures that might reduce relapse from exposure therapy for a number of psychological disorders. Some of these manipulations enhance the facilitatory cues from extinction that are present at test, others strengthen the extinction association (i.e., CS-no outcome), and yet others seem to work by a combination of these two processes.

Alternaria Induces STAT6-Dependent Acute Airway Eosinophilia and Epithelial FIZZ1 Expression That Promotes Airway Fibrosis and Epithelial Thickness

Journal of Immunology (Baltimore, Md. : 1950). Feb, 2012  |  Pubmed ID: 22327070

The fungal allergen, Alternaria, is specifically associated with severe asthma, including life-threatening exacerbations. To better understand the acute innate airway response to Alternaria, naive wild-type (WT) mice were challenged once intranasally with Alternaria. Naive WT mice developed significant bronchoalveolar lavage eosinophilia following Alternaria challenge when analyzed 24 h later. In contrast to Alternaria, neither Aspergillus nor Candida induced bronchoalveolar lavage eosinophilia. Gene microarray analysis of airway epithelial cell brushings demonstrated that Alternaria-challenged naive WT mice had a >20-fold increase in the level of expression of found in inflammatory zone 1 (FIZZ1/Retnla), a resistin-like molecule. Lung immunostaining confirmed strong airway epithelial FIZZ1 expression as early as 3 h after a single Alternaria challenge that persisted for ≥5 d and was significantly reduced in STAT6-deficient, but not protease-activated receptor 2-deficient mice. Bone marrow chimera studies revealed that STAT6 expressed in lung cells was required for epithelial FIZZ1 expression, whereas STAT6 present in bone marrow-derived cells contributed to airway eosinophilia. Studies investigating which cells in the nonchallenged lung bind FIZZ1 demonstrated that CD45(+)CD11c(+) cells (macrophages and dendritic cells), as well as collagen-1-producing CD45(-) cells (fibroblasts), can bind to FIZZ1. Importantly, direct administration of recombinant FIZZ1 to naive WT mice led to airway eosinophilia, peribronchial fibrosis, and increased thickness of the airway epithelium. Thus, Alternaria induces STAT6-dependent acute airway eosinophilia and epithelial FIZZ1 expression that promotes airway fibrosis and epithelial thickness. This may provide some insight into the uniquely pathogenic aspects of Alternaria-associated asthma.

The Safety Profile of Hemophilus Influenzae Type B-Neisseria Meningitidis Serogroups C and Y Tetanus Toxoid Conjugate Vaccine (HibMenCY)

Human Vaccines & Immunotherapeutics. Mar, 2012  |  Pubmed ID: 22327493

The safety profile of HibMenCY was compared with licensed Hib conjugate vaccines in a pooled analysis that included more than 8500 subjects who were administered a four-dose series of HibMenCY or commercially available Hib vaccines at 2, 4, 6 and 12-15 mo of age in two primary vaccination and two fourth dose Phase 3 studies. In all studies, HibMenCY or Hib vaccine was co-administered with age-appropriate, routinely recommended vaccines. In one primary and one fourth dose study (n = 4180), local and general symptoms were solicited using diary cards for 4 d after each dose. Serious adverse events (SAEs) and the occurrence of adverse events (AEs) indicating new onset of chronic disease (NOCD), rash, and conditions prompting Emergency Room (ER) visits were reported from dose 1 until 6 mo after dose 4. The incidences of solicited local and general symptoms were similar following HibMenCY and commercially available Hib vaccines. For some solicited symptoms (pain at the injection site and irritability), rates were lower in the HibMenCY group compared with the Hib control group (p-value 

Ribosome Display of Combinatorial Antibody Libraries Derived From Mice Immunised With Heat-Killed Xylella Fastidiosa and the Selection of MopB-Specific Single-Chain Antibodies

Applied and Environmental Microbiology. Feb, 2012  |  Pubmed ID: 22327580

Pierce's disease is a devastating lethal disease of Vitus vinifera grapevines caused by the bacterium Xylella fastidiosa. There is no cure for Pierce's disease and control is achieved predominantly by suppressing transmission of the glassy winged sharpshooter insect vector. We present a simple robust approach for the generation of panels of recombinant single chain antibodies against the surface exposed elements of X. fastidiosa that may have potential use in diagnosis and/or disease transmission blocking studies. In vitro combinatorial antibody ribosome display libraries were assembled from immunoglobulin transcripts rescued from the spleens of mice immunized with heat-killed X. fastidiosa. The libraries were used in a single round of selection against an outer-membrane protein MopB, resulting in the isolation of a panel of recombinant antibodies. The potential use of selected anti-MopB antibodies was demonstrated by the successful application of the 4XfMopB3 antibody in an ELISA, western blot and immunofluorescence assay. These immortalised in vitro recombinant single chain antibody libraries generated against heat killed X. fastidiosa are a resource for the Pierce's disease research community that may be readily accessed for the isolation of antibodies against a plethora of X. fastidiosa surface exposed antigenic molecules.

Improved Recovery of Prophylactic Inferior Vena Cava Filters in Trauma Patients: The Results of a Dedicated Filter Registry and Critical Pathway for Filter Removal

The Journal of Trauma. Feb, 2012  |  Pubmed ID: 22327980

: Temporary inferior vena cava filters (IVCF) are uniquely suited for trauma patients in whom the high risk of venous thromboembolism is transient. Currently, few "retrievable filters" are actually retrieved, with most published series documenting a retrieval rate between 20% and 50%. We sought to determine whether we could achieve a higher rate of retrieval with an improved process of care.

Sequential Duplex Ultrasound Screening for Proximal Deep Venous Thrombosis in Asymptomatic Patients with Acetabular and Pelvic Fractures Treated Operatively

The Journal of Trauma. Feb, 2012  |  Pubmed ID: 22327985

: Recent evidence-based practice guidelines recommend against routine ultrasound screening for proximal deep vein thrombosis (DVT) in asymptomatic pelvic fracture patients. However, the majority of trauma surgeons favor this practice. Furthermore, the timing of screening has been inconsistently described. The purpose of this study was to examine the utility of sequential scans in asymptomatic acetabular and pelvic fracture patients treated operatively.

In Pursuit of Scientific Excellence - Sex Matters

American Journal of Physiology. Heart and Circulatory Physiology. Feb, 2012  |  Pubmed ID: 22328082

n/a.

Decision Making by Humans in a Behavioral Task: Do Humans, Like Pigeons, Show Suboptimal Choice?

Learning & Behavior. Feb, 2012  |  Pubmed ID: 22328280

Consistent with human gambling behavior but contrary to optimal foraging theory, pigeons show a strong preference for an alternative with low probability and high payoff (a gambling-like alternative) over an alternative with a greater net payoff (Zentall & Stagner, Proceedings of the Royal Society B, 278, 1203-1208, 2011). In the present research, we asked whether humans would show suboptimal choice on a task involving choices with probabilities similar to those for pigeons. In Experiment 1, when we selected participants on the basis of their self-reported gambling activities, we found a significantly greater choice of the alternative involving low probability and high payoff (gambling-like alternative) than for a group that reported an absence of gambling activity. In Experiment 2, we found that when the inhibiting abilities of typical humans were impaired by a self-regulatory depletion manipulation, they were more likely to choose the gambling-like alternative. Taken together, the results suggest that this task is suitable for the comparative study of suboptimal decision-making behavior and the mechanisms that underlie it.

Fueled by Microtubules: Does Tubulin Dimer/polymer Partitioning Regulate Intracellular Metabolism?

Cytoskeleton (Hoboken, N.J.). Feb, 2012  |  Pubmed ID: 22328323

Microtubules or their subunits, tubulin dimers, interact with multiple components that contribute to intracellular metabolic pathways. Microtubules are required for insulin-dependent transport of glucose transporters (GLUT4) to the plasma membrane, they bind most glycolytic enzymes and are required for translation of the mRNA encoding hypoxia inducible factor -1α. Tubulin dimers bind the voltage dependent anion channel of the mitochondrial outer membrane; this channel functions in metabolite transport in and out of mitochondria. We hypothesize that tubulin partitioning between dimer and polymer pools regulates multiple steps in metabolism, where metabolic output is greatest when both tubulin dimers and microtubule polymers are present and reduced by drug treatments that disrupt this normal balance. Experimental evidence from these drug-induced changes in tubulin dimer/polymer partitioning supports our model for several metabolic steps. Signal transduction pathways that stabilize or destabilize microtubules can shift the normal ratio between unpolymerized and polymerized tubulin dimers, and one downstream consequence of this shift in tubulin partitioning could be a change in metabolic output. © 2012 Wiley Periodicals, Inc.

Patient-centered Imaging

Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology. Feb, 2012  |  Pubmed ID: 22328324

Immunophenotypic Alterations in Resident Immune Cells and Myocardial Fibrosis in the Aging Rhesus Macaque (Macaca Mulatta) Heart

Toxicologic Pathology. Feb, 2012  |  Pubmed ID: 22328408

The rhesus macaque (Macaca mulatta) is used extensively in translational biomedical research and drug development studies and is an important model of aging. Macaques often develop myocardial fibrosis with age, which can result in the loss of normal cardiac architecture with the expansion of the extracellular matrix and deposition of collagen. The etiology and pathogenesis of this pernicious process is poorly understood. Cardiac fibrosis was assessed using histologic and immunohistochemical techniques in cardiac tissue sections from 34 rhesus macaques. Overall left ventricular and left ventricular mid-myocardial interstitial/perivascular fibrosis were positively correlated with age (r = .6522, p < .0001 and r = .4704, p = .005, respectively). When divided into young (mean = 2.8 years), middle-aged (mean = 17.5 years), and advanced age (mean = 29.2 years) groups, immunophenotypic characterization of antigen presenting cells revealed differential expression of CD163 and DC-SIGN between the young and middle-aged groups compared to the advanced age group (p < .0001). HAM-56 expression decreased significantly in the advanced age cohort (p = .0021). The expression of CD8, CD163, and DC-SIGN correlated positively with age (r = .3999, p = .0191; r = .5676, p = .0005; r = .5245, p = .0014, respectively). These results show the importance of myocardial fibrosis as a common age-related pathology and additionally, alterations in T cell, macrophage, and dendritic cell phenotype in rhesus macaque myocardium are associated with age but unassociated with the fibrosis.

Corpus Callosum Damage Predicts Disability Progression and Cognitive Dysfunction in Primary-progressive MS After Five Years

Human Brain Mapping. Feb, 2012  |  Pubmed ID: 22328451

We aim to identify specific areas of white matter (WM) and grey matter (GM), which predict disability progression and cognitive dysfunction after five years in patients with primary-progressive multiple sclerosis (PPMS). Thirty-two patients with early PPMS were assessed at baseline and after five years on the Expanded Disability Status Scale (EDSS), and EDSS step-changes were calculated. At year five, a subgroup of 25 patients and 31 healthy controls underwent a neuropsychological assessment. Baseline imaging consisted of dual-echo (proton density and T2-weighted), T1-weighted volumetric, and diffusion tensor imaging. Fractional anisotropy (FA) maps were created, and fed into tract-based spatial statistics. To compensate for the potential bias introduced by WM lesions, the T1 volumes underwent a lesion-filling procedure before entering a voxel-based morphometry protocol. To investigate whether FA and GM volume predicted EDSS step-changes over five years and neuropsychological tests scores at five years, voxelwise linear regression analyses were performed. Lower FA in the splenium of the corpus callosum (CC) predicted a greater progression of disability over the follow-up. Lower FA along the entire CC predicted worse verbal memory, attention and speed of information processing, and executive function at five years. GM baseline volume did not predict any clinical variable. Our findings highlight the importance of damage to the interhemispheric callosal pathways in determining physical and cognitive disability in PPMS. Disruption of these pathways, which interconnect motor and cognitive networks between the two hemispheres, may result in a disconnection syndrome that contributes to long-term physical and cognitive disability. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.

Clarification Regarding the Practice Environment Checklist

Family Medicine. Feb, 2012  |  Pubmed ID: 22328485

Distress Resulting From Perceivers' Own Intimate Partner Violence Experiences Predicts Culpability Attributions Toward a Battered Woman on Trial for Killing Her Abuser: A Path Model

Journal of Interpersonal Violence. Feb, 2012  |  Pubmed ID: 22328653

Intimate partner violence (IPV) constitutes the majority of assaults against women in the United States, and greater than one third of female homicide victims are murdered by an intimate partner. In a small percentage of cases, battered women kill their abusers, and evidence of battering and its effects may be used to support a plea of self-defense in these cases. Prior research has shown that culpability attributions toward battered women who have killed their abusers are influenced by perceiver variables, including gender. The present study expands on this research by examining the influence of psychological distress resulting from perceivers' own IPV experiences-and the mechanisms of this influence-on their culpability attributions toward a battered woman defendant. Female undergraduates in the present sample (N = 154) read a vignette, adapted from an actual criminal case about a battered woman who had killed her abuser. Data supported a hypothesized path model, wherein participants reporting greater psychological distress resulting from IPV perpetrated against them perceived themselves more similar to the defendant, in turn empathized with her to a greater extent, and, in turn, attributed less legal culpability to her. Implications for future research are discussed.

Measurable Progress in Female Authorship in Otolaryngology

Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery. Feb, 2012  |  Pubmed ID: 22328701

Objective. To identify contemporary trends in female authorship in the otolaryngology literature.Study Design. Analysis of 4 otolaryngology journals.Setting. All articles published in Annals of Otology, Rhinology and Laryngology, Archives of Otolaryngology-Head and Neck Surgery, Laryngoscope, and Otolaryngology-Head and Neck Surgery in 2008 were reviewed and compared with prior data from 1978, 1988, and 1998.Subjects and Methods. Each published article's authorship panel was examined for the number of authors and each author's sex, degree, and the subspecialty area of publication. Year-to-year comparisons were conducted for the rates and characteristics of female authorship.Results. A total of 544, 629, 713, and 785 articles from 1978, 1988, 1998, and 2008, respectively, were analyzed. From 1998 to 2008, the overall percentage of female authors increased from 14.5% to 22.5% (P < .001). Similarly, the percentage of articles with a female first author increased from 12.9% to 21.3% (P < .001). Whereas previously pediatric otolaryngology had the highest female first author percentage (range, 6.9%-19.4%), in 2008 all other subspecialties demonstrated significant increases in female first author percentages: otology (18.6%), general (22.3%), head and neck (22.2%), plastics (18.9%), and pediatrics (19.4%) (P = .885). A significant number of female first authors continue to be nonphysicians (19.2% in 2008, P < .001).Conclusions. Female authorship has shown significant and steady increases in the otolaryngology literature, particularly in the past decade. Increased rates of publication from female otolaryngologists within most subspecialties have resulted in similar rates of publication across the subspecialties.

Youth Advisors Driving Action: Hearing the Youth Voice in Mental Health Systems of Care

Journal of Psychosocial Nursing and Mental Health Services. Feb, 2012  |  Pubmed ID: 22329621

The Children's Mental Health Initiative (CMHI) is funded by the Center for Mental Health Services within the Substance Abuse and Mental Health Services Administration. CMHI assists communities in developing comprehensive, coordinated services for children with serious emotional disturbances and their families. Broadly speaking, these systems are designed to be child centered, youth guided, family driven, community based, and culturally competent. To assure implementation of the "youth-guided" core value in the national evaluation, an advisory group of youth coordinator/youth teams representing communities across the country was developed. This group chose the name YADA-Youth Advisors Driving Action. YADA has made a substantive contribution to national evaluation efforts by bringing the youth perspective and voice to its audience at the community and national levels. This article describes YADA's founding and development, as well as related implications for psychosocial nurses.

Overperceiving Disease Cues: The Basic Cognition of the Behavioral Immune System

Journal of Personality and Social Psychology. Feb, 2012  |  Pubmed ID: 22329656

The behavioral immune system is designed to promote the detection and avoidance of potential sources of disease. Whereas previous studies of the behavioral immune system have provided insight into the types of heuristic cues used to identify disease carriers, the present research provides an understanding of the basic psychological processes involved in the detection of those cues. Across 4 studies, feeling vulnerable to disease, whether that feeling stemmed from dispositional tendencies or situational primes, facilitated a disease overperception bias-a tendency to overperceive people in the environment displaying heuristic disease cues. This disease overperception bias was observed in the outcomes of 2 cognitive processes: categorization and memory. When concerned about disease, participants set a lenient threshold for categorizing targets as displaying heuristic disease cues (e.g., obesity, old age). Additionally, concerns about disease led participants to set a lenient threshold for reporting on a recognition task that they had previously seen individuals displaying those disease cues. The present research provides insight into the basic cognitive mechanisms underlying the operation of the behavioral immune system. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Identification of Three Novel Hearing Loss Mouse Strains with Mutations in the Tmc1 Gene

The American Journal of Pathology. Feb, 2012  |  Pubmed ID: 22330676

We report the identification of three new mouse models, baringo, nice, and stitch, with recessively inherited sensorineural deafness due to novel mutations in the transmembrane channel-like gene 1 (Tmc1). These strains were generated by N-ethyl-N-nitrosourea mutagenesis. DNA sequence analysis revealed changes in c.545A>G, c.1345T>C, and c.1661G>T, causing p.Y182C, p.Y449H, and p.W554L amino acid substitutions in baringo, nice, and stitch mutants, respectively. The mutations affect amino acid residues that are evolutionarily conserved across species. Similar to the previously reported Beethoven Tmc1 mutant, both p.Y182C and p.W554L are located outside a predicted transmembrane domain, whereas the p.Y449H mutation resides in the predicted transmembrane domain 4. Homozygous stitch-mutant mice have severe hearing loss at the age of 4 weeks and are deaf by the age of 8 weeks, whereas both baringo and nice mutants are profoundly deaf at the age of 4 weeks. None of the strains displays signs of vestibular dysfunction. Scanning electron microscopy revealed degeneration of outer hair cells in the basal region of baringo, nice, and stitch mutants. Immunolocalization studies revealed expression of TMC1 protein in the hair cells, spiral ganglion neurons, supporting cells, and stria ligament in the inner ear. Reduced levels of TMC1 protein were observed in the spiral ligament of mutants when compared with wild-type animals. These three allelic mutants provide valuable models for studying nonsyndromic recessive sensorineural hearing loss (DFNB7/11) in humans.

Stereotactic Body Radiation Therapy in Spinal Metastases

International Journal of Radiation Oncology, Biology, Physics. Feb, 2012  |  Pubmed ID: 22330988

PURPOSE: Based on reports of safety and efficacy, stereotactic body radiotherapy (SBRT) for treatment of malignant spinal tumors was initiated at our institution. We report prospective results of this population at Mayo Clinic. MATERIALS AND METHODS: Between April 2008 and December 2010, 85 lesions in 66 patients were treated with SBRT for spinal metastases. Twenty-two lesions (25.8%) were treated for recurrence after prior radiotherapy (RT). The mean age of patients was 56.8 ± 13.4 years. Patients were treated to a median dose of 24 Gy (range, 10-40 Gy) in a median of three fractions (range, 1-5). Radiation was delivered with intensity-modulated radiotherapy (IMRT) and prescribed to cover 80% of the planning target volume (PTV) with organs at risk such as the spinal cord taking priority over PTV coverage. RESULTS: Tumor sites included 48, 22, 12, and 3 in the thoracic, lumbar, cervical, and sacral spine, respectively. The mean actuarial survival at 12 months was 52.2%. A total of 7 patients had both local and marginal failure, 1 patient experienced marginal but not local failure, and 1 patient had local failure only. Actuarial local control at 1 year was 83.3% and 91.2% in patients with and without prior RT. The median dose delivered to patients who experienced local/marginal failure was 24 Gy (range, 18-30 Gy) in a median of three fractions (range, 1-5). No cases of Grade 4 toxicity were reported. In 1 of 2 patients experiencing Grade 3 toxicity, SBRT was given after previous radiation. CONCLUSION: The results indicate SBRT to be an effective measure to achieve local control in spinal metastases. Toxicity of treatment was rare, including those previously irradiated. Our results appear comparable to previous reports analyzing spine SBRT. Further research is needed to determine optimum dose and fractionation to further improve local control and prevent toxicity.

EuroEcho and Other Imaging Modalities: Highlights

European Heart Journal Cardiovascular Imaging. Feb, 2012  |  Pubmed ID: 22331012

The annual meeting of the European Association of Echocardiography (EuroEcho and other Imaging Modalities) was held in Budapest, Hungary. In the present paper, we present a summary of the 'Highlights' session.

The Relationships Among Knowledge, Self-efficacy, Preparedness, Decisional Conflict, and Decisions to Participate in a Cancer Clinical Trial

Psycho-oncology. Feb, 2012  |  Pubmed ID: 22331643

BACKGROUND: Cancer clinical trials (CCTs) are important tools in the development of improved cancer therapies; yet, participation is low. Key psychosocial barriers exist that appear to impact a patient's decision to participate. Little is known about the relationship among knowledge, self-efficacy, preparation, decisional conflict, and patient decisions to take part in CCTs. OBJECTIVE: The purpose of this study was to determine if preparation for consideration of a CCT as a treatment option mediates the relationship between knowledge, self-efficacy, and decisional conflict. We also explored whether lower levels of decisional conflict are associated with greater likelihood of CCT enrollment. METHOD: In a pre-post test intervention study, cancer patients (N = 105) were recruited before their initial consultation with a medical oncologist. A brief educational intervention was provided for all patients. Patient self-report survey responses assessed knowledge, self-efficacy, preparation for clinical trial participation, decisional conflict, and clinical trial participation. RESULTS: Preparation was found to mediate the relationship between self-efficacy and decisional conflict (p = 0.003 for a test of the indirect mediational pathway for the decisional conflict total score). Preparation had a more limited role in mediating the effect of knowledge on decisional conflict. Further, preliminary evidence indicated that reduced decisional conflict was associated with increased clinical trial enrollment (p = 0.049). CONCLUSIONS: When patients feel greater CCT self-efficacy and have more knowledge, they feel more prepared to make a CCT decision. Reduced decisional conflict, in turn, is associated with the decision to enroll in a clinical trial. Our results suggest that preparation for decision-making should be a target of future interventions to improve participation in CCTs. Copyright © 2012 John Wiley & Sons, Ltd.

Phenotypic Information in Genomic Variant Databases Enhances Clinical Care and Research: The ISCA Consortium Experience

Human Mutation. Feb, 2012  |  Pubmed ID: 22331816

Whole genome analysis, now including whole genome sequencing, is moving rapidly into the clinical setting, leading to detection of human variation on a broader scale than ever before. Interpreting this information will depend on the availability of thorough and accurate phenotype information, and the ability to curate, store, and access data on genotype-phenotype relationships. This idea has already been demonstrated within the context of chromosome microarray (CMA) testing. The International Standards for Cytogenomic Arrays (ISCA) Consortium promotes standardization of variant interpretation for this technology through its initiatives, including the formation of a publicly available database housing clinical CMA data. Recognizing that phenotypic data is essential for the interpretation of genomic variants, the ISCA Consortium has developed tools to facilitate the collection of this data and its deposition in a standardized, structured format within the ISCA Consortium database. This rich source of phenotypic data can also be used within broader applications, such as developing phenotypic profiles of emerging genomic disorders, the identification of candidate regions for particular phenotypes, or the creation of tools for use in clinical practice. We summarize the ISCA experience as a model for ongoing efforts incorporating phenotype data with genotype data to improve the quality of research and clinical care in human genetics.

Gas-Liquid Segmented Flow Microfluidics for Screening Pd-Catalyzed Carbonylation Reactions

Chemistry (Weinheim an Der Bergstrasse, Germany). Feb, 2012  |  Pubmed ID: 22331821

Go with the (segmented) flow: A gas-liquid microfluidic reactor system has been developed to study Pd-catalyzed carbonylation reactions over a range of flow regimes and reaction conditions. The segmented gas-liquid flow regime, in comparison to annular flow, enables reactions to be studied over longer reaction times and without the buildup of unwanted Pd particles.

Pediatric Asthma Management

Respiratory Care. Feb, 2012  |  Pubmed ID: 22304805

Characterization of Nipah Virus from Outbreaks in Bangladesh, 2008-2010

Emerging Infectious Diseases. Feb, 2012  |  Pubmed ID: 22304936

Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes fatal encephalitis in humans. The initial outbreak of NiV infection occurred in Malaysia and Singapore in 1998-1999; relatively small, sporadic outbreaks among humans have occurred in Bangladesh since 2001. We characterized the complete genomic sequences of identical NiV isolates from 2 patients in 2008 and partial genomic sequences of throat swab samples from 3 patients in 2010, all from Bangladesh. All sequences from patients in Bangladesh comprised a distinct genetic group. However, the detection of 3 genetically distinct sequences from patients in the districts of Faridpur and Gopalganj indicated multiple co-circulating lineages in a localized region over a short time (January-March 2010). Sequence comparisons between the open reading frames of all available NiV genes led us to propose a standardized protocol for genotyping NiV; this protcol provides a simple and accurate way to classify current and future NiV sequences.

Evaluating Sex and Gender Competencies in the Medical Curriculum: A Case Study

Gender Medicine. Feb, 2012  |  Pubmed ID: 22304976

BACKGROUND: Sex and gender differences exist in the manifestation and prevalence of many conditions and diseases. Yet many clinician training programs neglect to integrate this information across their curricula. OBJECTIVE: This study aimed to measure the sex and gender medical knowledge of medical students enrolled in a program without an explicit directive to integrate sex and gender differences across a block system of core subjects. METHODS: A forced-choice instrument consisting of 35 multiple-choice and true or false questions was adapted from an evaluation tool used in the European Curriculum in Gender Medicine held at Charité Hospital, Berlin, in September 2010. RESULTS: Fourth-year (response rate 93%) and second-year (response rate 70%) students enrolled in Mayo Medical School completed the instrument. More than 50% of students in both classes indicated that topics related to sex and gender were covered in gynecology, cardiology, and pediatrics, and <20% of students indicated inclusion of such topics in nephrology, neurology, and orthopedics. More than twice as many second-year students indicated that topics dealing with sex and gender were included in immunology course material compared with fourth-year students. A consensus of written comments indicated that concepts of sex and gender-based medicine need to be embedded into existing curriculum, with an emphasis on clinically relevant information. CONCLUSIONS: Although this study represents only one medical school in the United States, information regarding sex and gender aspects of medicine is not consistently included in this curriculum without an explicit directive. These results can provide guidance for curriculum improvement to train future physicians.

Alleles That Modulate Late Life Hearing in Genetically Heterogeneous Mice

Neurobiology of Aging. Feb, 2012  |  Pubmed ID: 22305187

A genetically heterogeneous population of mice was tested for hearing at 8, 18, and 22 months by auditory brainstem response (ABR), and genotyped at 128 markers to identify loci that modulate late life hearing loss. Half of the test mice were exposed to noise for 2 hours at age 20 months. Polymorphisms affecting hearing at 18 months were noted on chromosomes 2, 3, 7, 10, and 15. Most of these loci had effects only on responses to 48 kHz stimuli, but a subset also influenced the auditory brainstem response at lower frequencies. Loci on chromosomes 4, 10, 12, and 14 had significant effects on hearing at 22 months in noise-exposed mice, and loci on chromosomes 10 and 11 had effects on mice not exposed to noise. Outer hair cell loss was modulated by polymorphisms on chromosomes 10, 11, 12, 17, and 19. Resistance to age-related hearing loss is thus modulated by a set of genetic effects, some age-specific, some frequency specific, some dependent on prior exposure to noise, and some of which compromise survival of cochlear hair cells.

Residency Interview Video Conferencing

Ophthalmology. Feb, 2012  |  Pubmed ID: 22305312

The Fourth INTERMACS Annual Report: 4,000 Implants and Counting

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. Feb, 2012  |  Pubmed ID: 22305376

The Fourth Annual Report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes and analyzes the first 5 years of patient and data collection. With more than 4,000 patients entered into the database, the evolution of pump technology, strategy at implant, and pre-implant patient profiles are chronicled. A risk factor analysis of the entire adult primary implant population is provided, and the recent composition of patient profiles is examined. Current actuarial survival with continuous-flow pumps exceeds 80% at 1 year and 70% at 2 years.

Age-related Somatic Structural Changes in the Nuclear Genome of Human Blood Cells

American Journal of Human Genetics. Feb, 2012  |  Pubmed ID: 22305530

Structural variations are among the most frequent interindividual genetic differences in the human genome. The frequency and distribution of de novo somatic structural variants in normal cells is, however, poorly explored. Using age-stratified cohorts of 318 monozygotic (MZ) twins and 296 single-born subjects, we describe age-related accumulation of copy-number variation in the nuclear genomes in vivo and frequency changes for both megabase- and kilobase-range variants. Megabase-range aberrations were found in 3.4% (9 of 264) of subjects ≥60 years old; these subjects included 78 MZ twin pairs and 108 single-born individuals. No such findings were observed in 81 MZ pairs or 180 single-born subjects who were ≤55 years old. Recurrent region- and gene-specific mutations, mostly deletions, were observed. Longitudinal analyses of 43 subjects whose data were collected 7-19 years apart suggest considerable variation in the rate of accumulation of clones carrying structural changes. Furthermore, the longitudinal analysis of individuals with structural aberrations suggests that there is a natural self-removal of aberrant cell clones from peripheral blood. In three healthy subjects, we detected somatic aberrations characteristic of patients with myelodysplastic syndrome. The recurrent rearrangements uncovered here are candidates for common age-related defects in human blood cells. We anticipate that extension of these results will allow determination of the genetic age of different somatic-cell lineages and estimation of possible individual differences between genetic and chronological age. Our work might also help to explain the cause of an age-related reduction in the number of cell clones in the blood; such a reduction is one of the hallmarks of immunosenescence.

Mass Transport Characteristics of Alkyl Amines in a Water/n-decane System

Journal of Colloid and Interface Science. Jan, 2012  |  Pubmed ID: 22305575

Water-in-decane emulsions can be applied as reaction system for the precipitation of nanoparticles. Herein the precipitation reaction is induced once an oil as well as water soluble compound (here: alkyl amines) diffuses from the continuous oil phase into a water based droplet, loaded with the reaction partner. Thus, the mass transfer and adsorption characteristics of the alkyl amine at the interface are key parameters to understand particle formation in emulsion droplets. For this reason, the effective diffusion coefficients and the interfacial tension of different alkyl amines in a water/n-decane system were estimated. Furthermore, emulsifiers necessary for the stability of the emulsion might represent a diffusion barrier. In order to determine its influence, diffusion experiments were also conducted in the presence of emulsifier. The effective diffusion coefficients were measured using an adapted photometric method. To identify relevant adsorption characteristics of the water/n-decane/alkyl amine systems, the interfacial tension was studied with the pendant drop technique. According to the results, we can draw three conclusions: First, the effective diffusion coefficient depends on the molecular structure of the amines. Second, regarding our materials, the surface activity and surface coverage proved to be a governing parameter to describe differences in the transport mechanism. And third, the presence of additional surface active compounds leads to a decrease of the effective diffusion coefficient.

Characterisation of Alkyl Amines at the Water/air Surface with the Drop and Bubble Profile Analysis Tensiometry

Journal of Colloid and Interface Science. Jan, 2012  |  Pubmed ID: 22305576

Pendant drop and buoyant bubble methods have been used to study the surface characteristics of alkyl amines at the water/air surface. The investigated alkyl amines, triethylamine and octylamine, showed unusual changes in the surface tension as a function of time: an initially steep drop and a subsequent steady increase in the surface tension until a value close to the one of the pure water/air system was observed. This phenomenon is explained by the evaporation of the alkyl amines, for which several sets of experiments have been conducted with the pendant drop and buoyant bubble methods. Using an appropriate experimental protocol, the equilibrium adsorption behaviour of the two amines can be quantitatively measured.

Detection of Cryptosporidium in Miniaturised Fluidic Devices

Water Research. Jan, 2012  |  Pubmed ID: 22305660

Contamination of drinking water with the protozoan pathogen, Cryptosporidium, represents a serious risk to human health due to the low infectious dose and the resistance of this parasite to chlorine disinfection. Therefore, several countries have legislated for the frequent monitoring of drinking water for Cryptosporidium presence. Existing approved monitoring protocols are however time-consuming and do not provide essential information on the species, virulence or viability of detected oocysts. Rapid, more information-rich and automatable systems for Cryptosporidium detection are highly sought-after, and numerous miniaturised devices have been developed to address this need. This review article aims to summarise the state-of-the-art and compare the performance of these systems in terms of detection limit, ability to determine species, viability and performance in the presence of interferents. Finally, conclusions are drawn with regard to the most promising methods and directions of future research.

Sputum Matrix Metalloproteinase-12 in Patients with Chronic Obstructive Pulmonary Disease and Asthma: Relationship to Disease Severity

The Journal of Allergy and Clinical Immunology. Feb, 2012  |  Pubmed ID: 22305682

BACKGROUND: Matrix metalloproteinase (MMP)-12 has been implicated in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and asthma. The influence of disease severity on sputum MMP-12 concentrations and activity is not known. OBJECTIVES: We sought to examine the relationship between disease severity assessed by means of lung function and computed tomography (CT) and induced sputum MMP-12 concentrations and activity in patients with asthma and COPD. METHODS: In 208 subjects (109 asthmatic patients, smokers and never smokers, mild, moderate, and severe; 53 patients with COPD, smokers and exsmokers, mild, moderate, and severe; and 46 healthy control subjects, smokers and never smokers), we measured induced sputum MMP-12 concentrations (ELISA) and enzyme activity (fluorescence resonance energy transfer), sputum cell MMP12 mRNA expression (quantitative PCR [qPCR]), diffusing capacity for carbon monoxide (Dlco), and CT assessment of emphysema (percentage of low-attenuation areas at less -950 Hounsfield units). RESULTS: Sputum MMP-12 concentrations are greater in patients with COPD and smokers with asthma than in healthy nonsmokers (P = .003 and P = .035, respectively) but similar to those seen in healthy smokers. In patients with COPD, disease severity, when measured by means of CT-assessed emphysema, but not by means of spirometry or Dlco values, is directly associated with sputum MMP-12 concentrations and activity. In the asthma groups there is no significant association between disease severity and sputum MMP-12 concentrations or activity. CONCLUSIONS: Sputum MMP-12 concentrations and activity in patients with COPD are directly associated with the extent of emphysema measured by means of CT. This finding supports a role for MMP-12 in the pathogenesis of COPD and might suggest that blocking MMP-12 activity in patients with COPD could prevent the further development of emphysema.

Aggregating Traditional Cardiovascular Disease Risk Factors to Assess the Cardiometabolic Health of Childhood Cancer Survivors: An Analysis from the Cardiac Risk Factors in Childhood Cancer Survivors Study

American Heart Journal. Feb, 2012  |  Pubmed ID: 22305850

Childhood cancer survivors are at increased risk of cardiovascular disease (CVD), which may be associated with traditional CVD risk factors. We used CVD risk aggregation instruments to describe survivor cardiometabolic health and compared their results with sibling controls.

Attention-deficit/hyperactivity Disorder Comorbidity in a Sample of Veterans with Posttraumatic Stress Disorder

Comprehensive Psychiatry. Feb, 2012  |  Pubmed ID: 22305866

This study examined attention-deficit/hyperactivity disorder (ADHD) comorbidity in military veterans with a high prevalence of posttraumatic stress disorder (PTSD) and evaluated the relationships between the 2 disorders and exposure to traumatic events. The sample included 222 male and female military veterans who were administered structured clinical interviews based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Results show that 54.5% met the criteria for current PTSD, 11.5% of whom also met the criteria for current adult ADHD. Level of trauma exposure and ADHD severity were significant predictors of current PTSD severity. Evaluation of the underlying structure of symptoms of PTSD and ADHD using confirmatory factor analysis yielded a best-fitting measurement model that comprised 4 PTSD factors and 3 ADHD factors. Standardized estimates of the correlations among PTSD and ADHD factors suggested that the largest proportion of shared variance underlying PTSD-ADHD comorbidity is related to problems with modulating arousal levels that are common to both disorders (ie, hyperarousal and hypoarousal).

Using the Learning Log to Encourage Reflective Practice

Education for Primary Care : an Official Publication of the Association of Course Organisers, National Association of GP Tutors, World Organisation of Family Doctors. Jan, 2012  |  Pubmed ID: 22306147

Ex Vivo Fucosylation Improves Human Cord Blood Engraftment in NOD-SCID IL-2Rγnull (NSG) Mice

Experimental Hematology. Feb, 2012  |  Pubmed ID: 22306295

Delayed engraftment remains a major hurdle following cord blood (CB) transplantation. It may be due, at least in part, to low fucosylation of cell surface molecules important for homing to the BM microenvironment. Since fucosylation of specific cell surface ligands is required before effective interaction with selectins expressed by the BM microvasculature can occur, a simple 30 minute ex vivo incubation of CB HPC with fucosyltransferase (FT) - VI and its substrate (GDP-fucose) was performed to increase levels of fucosylation. The physiologic impact of CB HPC hypo-fucosylation was investigated in vivo in NOD-SCID IL-2Rγ(null) (NSG) mice. By isolating fucosylated and non-fucosylated CD34(+) cells from CB we show that only fucosylated CD34(+) cells are responsible for engraftment in NSG mice. Further, since the proportion of CD34(+) cells that are fucosylated in CB is significantly less than in BM and PB, we hypothesize that these combined observations might explain, at least in part, the delayed engraftment observed following CB transplantation. Since engraftment appears to be correlated with the fucosylation of CD34(+) cells, we hypothesized that increasing the proportion of CD34(+) cells that are fucosylated would improve CB engraftment. Ex vivo treatment with fucosyltransferase (FT)-VI significantly increases the levels of CD34(+) fucosylation and, as hypothesized, this was associated with improved engraftment. Ex vivo fucosylation did not alter the biodistribution of engrafting cells, or pattern of long-term, multi-lineage, multi-tissue engraftment. We propose that ex vivo fucosylation will similarly improve the rate and magnitude of engraftment for CB transplant recipients in a clinical setting.

Small-molecule-induced DNA Damage Identifies Alternative DNA Structures in Human Genes

Nature Chemical Biology. 2012  |  Pubmed ID: 22306580

Guanine-rich DNA sequences that can adopt non-Watson-Crick structures in vitro are prevalent in the human genome. Whether such structures normally exist in mammalian cells has, however, been the subject of active research for decades. Here we show that the G-quadruplex-interacting drug pyridostatin promotes growth arrest in human cancer cells by inducing replication- and transcription-dependent DNA damage. A chromatin immunoprecipitation sequencing analysis of the DNA damage marker γH2AX provided the genome-wide distribution of pyridostatin-induced sites of damage and revealed that pyridostatin targets gene bodies containing clusters of sequences with a propensity for G-quadruplex formation. As a result, pyridostatin modulated the expression of these genes, including the proto-oncogene SRC. We observed that pyridostatin reduced SRC protein abundance and SRC-dependent cellular motility in human breast cancer cells, validating SRC as a target of this drug. Our unbiased approach to define genomic sites of action for a drug establishes a framework for discovering functional DNA-drug interactions.

Translating Stem Cell Therapies to the Clinic

Neuroscience Letters. Jan, 2012  |  Pubmed ID: 22306614

One of the most remarkable advances in translational neuroscience of the last few years has been the emergence of cell-based approaches for a wide range of neurological disease and injuries. Molecular approaches designed for the treatment of neurological injuries and insults such as stroke, spinal cord injury and multiple sclerosis have proven to be of limited effectiveness in large part because it has become clear that there is not a single "magic bullet" that allows for neuronal survival, axonal regeneration and/or remyelination. Rather the pathogenesis of insults such as stroke, spinal cord injury and MS are complex, engaging multiple cell types and signaling pathways and as a result require the simultaneous intervention in multiple arenas in order to facilitate functional recovery. Cell therapies, because of their inherent complexity offer the opportunity to intervene at several points in the pathological process and thus may provide a more effective treatment strategy. Among the multiple cell types assessed as therapeutic treatment for neural insults, stem cells have emerged as possibly the most effective class. The particular characteristics of stem cells, namely their ability to self-renew and generate multiple cell types promoted their use as sources of cell replacement in the injured CNS. It is likely, however that the major advance that stem cells have over more restricted cell types is their ability to modulate the responses of the immune system and to influence endogenous tissue stem cells to accentuate repair. While preclinical studies are moving extremely rapidly, the effective translation of these studies to the clinical arena remains extremely challenging.

Disease-Associated Polyglutamine Stretches in Monomeric Huntingtin Adopt a Compact Structure

Journal of Molecular Biology. Jan, 2012  |  Pubmed ID: 22306738

Abnormal polyglutamine (polyQ) tracts are the only common feature in nine proteins that each cause a dominant neurodegenerative disorder. In Huntington's disease, tracts longer than 36 glutamines in the protein huntingtin (htt) cause degeneration. In situ, monoclonal antibody 3B5H10 binds to different htt fragments in neurons in proportion to their toxicity. Here, we determined the structure of 3B5H10 Fab to 1.9 Å resolution by X-ray crystallography. Modeling demonstrates that the paratope forms a groove suitable for binding two β-rich polyQ strands. Using small-angle X-ray scattering, we confirmed that the polyQ epitope recognized by 3B5H10 is a compact two-stranded hairpin within monomeric htt and is abundant in htt fragments unbound to antibody. Thus, disease-associated polyQ stretches preferentially adopt compact conformations. Since 3B5H10 binding predicts degeneration, this compact polyQ structure may be neurotoxic.

Cancer Risks Associated with External Radiation from Diagnostic Imaging Procedures

CA: a Cancer Journal for Clinicians. Feb, 2012  |  Pubmed ID: 22307864

The 600% increase in medical radiation exposure to the US population since 1980 has provided immense benefit, but increased potential future cancer risks to patients. Most of the increase is from diagnostic radiologic procedures. The objectives of this review are to summarize epidemiologic data on cancer risks associated with diagnostic procedures, describe how exposures from recent diagnostic procedures relate to radiation levels linked with cancer occurrence, and propose a framework of strategies to reduce radiation from diagnostic imaging in patients. We briefly review radiation dose definitions, mechanisms of radiation carcinogenesis, key epidemiologic studies of medical and other radiation sources and cancer risks, and dose trends from diagnostic procedures. We describe cancer risks from experimental studies, future projected risks from current imaging procedures, and the potential for higher risks in genetically susceptible populations. To reduce future projected cancers from diagnostic procedures, we advocate the widespread use of evidence-based appropriateness criteria for decisions about imaging procedures; oversight of equipment to deliver reliably the minimum radiation required to attain clinical objectives; development of electronic lifetime records of imaging procedures for patients and their physicians; and commitment by medical training programs, professional societies, and radiation protection organizations to educate all stakeholders in reducing radiation from diagnostic procedures. CA Cancer J Clin 2012. © 2012 American Cancer Society.

Comparison of Right Ventricular Longitudinal Strain Imaging, Tricuspid Annular Plane Systolic Excursion, and Cardiac Biomarkers for Early Diagnosis of Cardiac Involvement and Risk Stratification in Primary Systematic (AL) Amyloidosis: a 5-year Cohort Study

European Heart Journal Cardiovascular Imaging. Feb, 2012  |  Pubmed ID: 22307866

AIMS: To determine the role of assessing right ventricular (RV) function, using standard echocardiography and Doppler myocardial imaging (DMI), in the early diagnosis of cardiac amyloidosis and in the prediction of mortality. METHODS AND RESULTS: Patients with primary systemic (AL) amyloidosis seen at our institution from 1 February 2004 through 31 October 2005 (N = 249) were categorized by left ventricular thickness and E' velocity and compared with 38 age- and sex-matched controls. Standard echocardiographic and DMI examination were used to measure echocardiographic parameters of RV function: systolic tissue velocity, strain rate, and strain were determined for basal and middle RV free wall segments. Patients were followed up for the endpoint of mortality. RV tricuspid annular plane systolic excursion (TAPSE) and all DMI measurements were lower in patients with AL amyloidosis and normal echocardiography results (AL-normal-echo group) than controls. A bivariate model including strain of the basal segment of the RV free wall and TAPSE was the best for distinguishing AL-normal-echo patients from controls. Male sex [hazard ratio (HR), 2.2; P= 0.005], brain natriuretic peptide levels (HR 1.4; P= 0.003), troponin T levels (HR 1.6; P= 0.01), pleural effusion (HR 3.6; P< 0.001), E/A ratio (HR 1.3; P= 0.006), RV systolic pressure (HR 1.02; P= 0.01), and RV strain rate of the middle segment (HR 1.3; P= 0.02) were independent predictors of death. CONCLUSION: DMI measures of the RV can identify early impairment of cardiac function or stratify risk of death in patients with AL amyloidosis. Further studies with longer follow-up are warranted to confirm these results.

Implications for Genotype-phenotype Predictions in Townes-Brocks Syndrome: Case Report of a Novel SALL1 Deletion and Review of the Literature

American Journal of Medical Genetics. Part A. Feb, 2012  |  Pubmed ID: 22308078

Townes-Brocks syndrome (TBS) is a well-described genetic syndrome characterized by anal, ear, and thumb anomalies and variable expressivity. Over 60 nonsense and frameshift mutations have been identified in SALL1, the zinc finger transcription factor causing TBS, and are proposed to cause disease via a dominant negative mechanism. In contrast, only four deletions have been described, with mild phenotypes reported as a result of haploinsufficiency. We report on a family with features of TBS in whom a novel 149 kb deletion spanning the SALL1 gene was identified by high resolution cytogenetics SNP microarray. We review the available genotype-phenotype information for all known truncating mutations and deletions. Taken together, they do not support the correlation of SALL1 deletions with a milder TBS phenotype and highlight a need for more robust clinical phenotyping combined with investigation of mutational mechanism. © 2012 Wiley Periodicals, Inc.

Severe Mammal Declines Coincide with Proliferation of Invasive Burmese Pythons in Everglades National Park

Proceedings of the National Academy of Sciences of the United States of America. Feb, 2012  |  Pubmed ID: 22308381

Invasive species represent a significant threat to global biodiversity and a substantial economic burden. Burmese pythons, giant constricting snakes native to Asia, now are found throughout much of southern Florida, including all of Everglades National Park (ENP). Pythons have increased dramatically in both abundance and geographic range since 2000 and consume a wide variety of mammals and birds. Here we report severe apparent declines in mammal populations that coincide temporally and spatially with the proliferation of pythons in ENP. Before 2000, mammals were encountered frequently during nocturnal road surveys within ENP. In contrast, road surveys totaling 56,971 km from 2003-2011 documented a 99.3% decrease in the frequency of raccoon observations, decreases of 98.9% and 87.5% for opossum and bobcat observations, respectively, and failed to detect rabbits. Road surveys also revealed that these species are more common in areas where pythons have been discovered only recently and are most abundant outside the python's current introduced range. These findings suggest that predation by pythons has resulted in dramatic declines in mammals within ENP and that introduced apex predators, such as giant constrictors, can exert significant top-down pressure on prey populations. Severe declines in easily observed and/or common mammals, such as raccoons and bobcats, bode poorly for species of conservation concern, which often are more difficult to sample and occur at lower densities.

Optically Monitoring Voltage in Neurons by Photo-induced Electron Transfer Through Molecular Wires

Proceedings of the National Academy of Sciences of the United States of America. Feb, 2012  |  Pubmed ID: 22308458

Fluorescence imaging is an attractive method for monitoring neuronal activity. A key challenge for optically monitoring voltage is development of sensors that can give large and fast responses to changes in transmembrane potential. We now present fluorescent sensors that detect voltage changes in neurons by modulation of photo-induced electron transfer (PeT) from an electron donor through a synthetic molecular wire to a fluorophore. These dyes give bigger responses to voltage than electrochromic dyes, yet have much faster kinetics and much less added capacitance than existing sensors based on hydrophobic anions or voltage-sensitive ion channels. These features enable single-trial detection of synaptic and action potentials in cultured hippocampal neurons and intact leech ganglia. Voltage-dependent PeT should be amenable to much further optimization, but the existing probes are already valuable indicators of neuronal activity.

Culex Flavivirus and West Nile Virus in Culex Quinquefasciatus Populations in the Southeastern United States

Journal of Medical Entomology. Jan, 2012  |  Pubmed ID: 22308785

Little is known of the interactions between insect-only flaviviruses and other arboviruses in their mosquito hosts, or the potential public health significance of these associations. The specific aims of this study were to describe the geographic distribution, prevalence, and seasonal infection rates of Culex flavivirus (CxFV) and West Nile virus (WNV) in Culex quinquefasciatus Say in the Southeastern United States, investigate the potential association between CxFV and WNV prevalence in Cx. quinquefasciatus and describe the phylogenetic relationship among CxFV and WNV isolates from the Southeastern United States and around the world. Using ArboNET records, 11 locations were selected across Georgia, Mississippi, and Louisiana that represented a range of WNV human case incidence levels. Cx. quinquefasciatus were trapped weekly throughout the summer of 2009 and pools were screened for flavivirus RNA by reverse transcriptase polymerase chain reaction. Cx. quinquefasciatus from Georgia had significantly higher CxFV infection rates than either Mississippi or Louisiana. CxFV was not detected in Mississippi after July, and no CxFV was detected in Cx. quinquefasciatus in Louisiana. In Georgia, CxFV infection rates were variable between and within counties and over time. WNV infection rates were not significantly different across states or months, and WNV sequences from all three states were identical to each other in the envelope and NS5 gene regions. Phylogenetically, NS5 and E gene sequences from Georgia CxFV isolates clustered with CxFV from Japan, Iowa, and Texas. Multiple CxFV genetic variants were found circulating simultaneously in Georgia. No evidence was found supporting an association between WNV and CxFV infection prevalence in Cx. quinquefasciatus.

Multi-directional in Vivo Tensile Skin Stiffness Measurement for the Design of a Reproducible Tensile Strain Elastography Protocol

Skin Research and Technology : Official Journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI). Feb, 2012  |  Pubmed ID: 22309091

BACKGROUND/AIMS: Elastography is a promising new medical imaging modality, displaying spatial distribution of biomechanical properties such as local tissue strain response to an applied stress. To develop a reproducible test protocol for skin elastography, the effect of various parameters on skin stiffness measurements was investigated. METHODS: The parameters investigated were: history of skin loading before test loading (preconditioning), direction of test loading (anisotropy) and posture (pre-stress). If a sample of skin is loaded, its stiffness will temporarily change. Finally, the reproducibility of skin stiffness and anisotropy measurements, using the developed techniques, was investigated. RESULTS: By measuring how the stiffness changed with different time delays between loading cycles, the time required for healthy skin to return to its original pre-loaded state was in the region of 125 s. A second finding, which supports and extends previous work, was that skin stiffness varied with direction, by an approximate factor of 2, and that anisotropy was less apparent with preconditioned skin than non-preconditioned skin. Study of the effect of posture showed that care needs to be taken over which stiffness measure is used. For example, measurement of the load at a given displacement was found to be highly dependent on posture, whereas measurement of the phase III stiffness was independent of posture. CONCLUSION: It was shown that when the measurement variables and methods of analysis were standardised, skin stiffness could be measured reproducibly enough to distinguish between the stiffest and softest directions, and that these methods allowed formation of skin elastograms free from confounding influences.

After-School Physical Activity and Eating Behaviors of Middle School Students in Relation to Adult Supervision

Journal of Nutrition Education and Behavior. Feb, 2012  |  Pubmed ID: 22309738

OBJECTIVE: Examine after-school activity patterns, eating behaviors, and social environment of overweight and normal weight middle school students. DESIGN: Eating and physical activity behaviors of 141 students, ages 10-14, were monitored. Students completed a diary documenting type of activity, location, adult supervision, accompanying participants, and eating habits from 3:00 pm-12:00 am. SETTING: Three middle schools, grades 6-8. MAIN OUTCOME MEASURES: Body mass index, estimated energy expenditure, eating behavior, active time, sedentary time, supervised time. ANALYSIS: t tests, ANOVA, chi-square, correlation coefficients. Significance set at P < .05. RESULTS: Children spent 76% of time sedentary, and 85% of sedentary time was under adult supervision (r = 0.76). Active time related to time with friends (r = 0.64) and family (r = 0.46). Children spent 40% of eating time consuming unhealthful food, and adults supervised 86% of children's eating. Overweight and normal weight children were similarly active (335 ± 156 vs 373 ± 194 counts per minute). Overweight girls spent more eating time (77%) eating healthfully than overweight boys (57%). CONCLUSIONS AND IMPLICATIONS: Children should be given access to healthful food and encouraged to eat healthfully when alone and with friends. Adults should be more physically engaged with children. Children should be encouraged to eat under adult supervision and with their families.

Industrial Toxicants and Parkinson's Disease

Neurotoxicology. Jan, 2012  |  Pubmed ID: 22309908

The exposure of the human population to environmental contaminants is recognized as a significant contributing factor for the development of Parkinson's disease (PD) and other forms of parkinsonism. While pesticides have repeatedly been identified as risk factors for PD, these compounds represent only a subset of environmental toxicants that we are exposed to on a regular basis. Thus, non-pesticide contaminants, such as metals, solvents, and other organohalogen compounds have also been implicated in the clinical and pathological manifestations of these movement disorders and it is these non-pesticide compounds that are the subject of this review. As toxic exposures to these classes of compounds can result in a spectrum of PD or PD-related disorders, it is imperative to appreciate shared clinico-pathological characteristics or mechanisms of action of these compounds in order to further delineate the resultant disorders as well as identify improved preventive strategies or therapeutic interventions.

Keeping Current: Clinical Decision Support Systems

Journal of Dental Hygiene : JDH / American Dental Hygienists' Association. 2012  |  Pubmed ID: 22309925

Aberrant Iliac Artery: Far Lateral Lumbosacral Surgical Anatomy

Orthopedics. 2012  |  Pubmed ID: 22310424

A 44-year-old man presented after 3 weeks of progressively worsening atraumatic onset pain in the right anteromedial thigh. The pain was sharp and radiated to the anteromedial shin and medial foot. The patient had no associated weakness, numbness, or bowel/bladder dysfunction. Nonsteroidal anti-inflammatory, pain, and neuropathic-relieving drugs had limited effect. He underwent interlaminar injections, which provided transient relief of his shin symptoms.After conservative management failed, a spine surgeon (not affiliated with our practice) recommended an anterior lumbar interbody fusion via far lateral approach. The patient presented to our spine clinic for a second opinion. Closed magnetic resonance imaging revealed an aberrant iliac artery impinging on the lumbar plexus and a foraminal herniation at L4-L5 on the right, an orientation more lateral than expected or seen on the contralateral side. We recommended physical therapy that focused on core strength and adequate stretching prior to considering surgery. The patient's symptoms have since resolved. Common iliac artery anomalies are rare. No known incidence exists. The finding in this case was incidental and, if missed, could have led to vascular compromise. To prevent such an injury during minimally invasive (transpsoas lateral approach) spine surgery, we recommend careful examination of radiographs for aberrant vessels.

Understanding the Role of Percutaneous Biopsy in the Management of Patients with a Small Renal Mass

Urology. Feb, 2012  |  Pubmed ID: 22310755

To evaluate patient and tumor characteristics associated with percutaneous renal mass biopsy (RMB) among patients with small renal masses (SRMs) and assessed the impact on clinical decision-making.

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Urology. Feb, 2012  |  Pubmed ID: 22310757

Item Response Theory Reveals Variability of Functional Impairment Within Clinical Dementia Rating Scale Stages

Dementia and Geriatric Cognitive Disorders. Feb, 2012  |  Pubmed ID: 22311305

Background/Aims:To investigate whether an item response theory (IRT) approach to measuring variations of dementia severity within Clinical Dementia Rating (CDR) stages is associated with activities of daily living (ADLs). Methods: IRT estimates of dementia severity within CDR stages in 1,181 patients were correlated with ADLs and analyzed. Results: IRT-determined dementia severity was significantly correlated with ADLs in three of four impaired dementia stages. Conclusion: An IRT approach shows considerable advantages over traditional scoring practices of the CDR not only because it increases precision in dementia measurement, but also because it enables one to discover more precise associations with functional outcomes such as ADLs.

Pulmonary Veno-occlusive Disease: a Misnomer?

Pediatric Radiology. Feb, 2012  |  Pubmed ID: 22311592

Pulmonary veno-occlusive disease (PVOD) is a rare entity with non-specific signs and symptoms and is nearly always associated with a dismal prognosis. This review will first consider pulmonary hypertension in general and then will focus on PVOD specifically with particular attention to the pathophysiology of the disease. Classically PVOD is described as a disease primarily involving obstructed venules, with the arterial side of the circulation involved to a lesser degree. This article discusses the demographics of affected individuals; the ways in which an accurate diagnosis can be made, including imaging features; predisposing diseases and associated disorders; and potential treatment.

Application of 2D DIGE in Animal Proteomics

Methods in Molecular Biology (Clifton, N.J.). 2012  |  Pubmed ID: 22311774

Two-dimensional electrophoresis (2 DE) is one of the most important proteomic tools and allows studying the complexity of proteomes of different origin. This chapter describes a setup for 2D DIGE with minimal labeling for qualitative and quantitative applications. It relies on homemade gels of medium size and in our hands has been found useful for a wide variety of separation problems involving complex protein mixtures of animal or human origin. The basic method is given for serum proteins of different species, but with minor modifications the method may be easily adapted to other sample materials (other body fluids, cells, tissues), conditions, or size. Examples are given for simple pattern comparisons (e.g., quality control, fast comparison of just two samples) as well as for quantitative applications to larger sample sets.

Vignette-based Study of Ovarian Cancer Screening: Do U.s. Physicians Report Adhering to Evidence-based Recommendations?

Annals of Internal Medicine. Feb, 2012  |  Pubmed ID: 22312138

Background: No professional society or group recommends routine ovarian cancer screening, yet physicians' enthusiasm for several cancer screening tests before benefit has been proven suggests that some women may be exposed to potential harms. Objective: To provide nationally representative estimates of physicians' reported nonadherence to recommendations against ovarian cancer screening. Design: Cross-sectional survey of physicians offering women's primary care. The 12-page questionnaire contained a woman's annual examination vignette and questions about offers or orders for transvaginal ultrasonography (TVU) and cancer antigen 125 (CA-125). Setting: United States. Participants: 3200 physicians randomly sampled equally from the 2008 American Medical Association Physician Masterfile lists of family physicians, general internists, and obstetrician-gynecologists; 61.7% responded. After exclusions, 1088 respondents were included; their responses were weighted to represent the specialty distribution of practicing U.S. physicians nationally. Measurements: Reported nonadherence to screening recommendations (defined as sometimes or almost always ordering screening TVU or CA-125 or both). Results: Twenty-eight percent (95% CI, 24.5% to 32.9%) of physicians reported nonadherence to screening recommendations for women at low risk for ovarian cancer; 65.4% (CI, 61.1% to 69.4%) did so for women at medium risk for ovarian cancer. Six percent (CI, 4.4% to 8.9%) reported routinely ordering or offering ovarian cancer screening for low-risk women, as did 24.0% (CI, 20.5% to 28.0%) for medium-risk women (P ≤ 0.001). Thirty-three percent believed TVU or CA-125 was an effective screening test. In adjusted analysis, actual and physician-perceived patient risk, patient request for ovarian cancer screening, and physician belief that TVU or CA-125 was an effective screening test were the strongest predictors of physician-reported nonadherence to published recommendations. Limitation: The results are limited by their reliance on survey methods; there may be respondent-nonrespondent bias. Conclusion: One in 3 physicians believed that ovarian cancer screening was effective, despite evidence to the contrary. Substantial proportions of physicians reported routinely offering or ordering ovarian cancer screening, thereby exposing women to the documented risks of these tests. Primary Funding Source: Centers for Disease Control and Prevention and the National Cancer Institute.

Single Course of Antenatal Steroids Did Not Alter Cortisol in Preterm Infants to 18 Months

Acta Paediatrica (Oslo, Norway : 1992). Feb, 2012  |  Pubmed ID: 22313364

Aims:  To determine if a single course of antenatal dexamethasone alters resting cortisol at 3, 8 and 18 months corrected age in preterm infants. Methods:  Preterm infants born ≤32 weeks gestational age were recruited during 2001-2004 from a single neonatal intensive care unit. Resting salivary cortisol was collected at least once at 3, 8 and 18 months corrected age in a longitudinal cohort. A mixed-effects repeated measures analysis was used to accommodate cases with less than complete follow-up. Results:  133 infants were included in the present study, contributing 266 cortisol samples. Of these, 107 infants had been exposed to a single course of antenatal dexamethasone and 26 not-exposed to antenatal steroids. There was no significant main effect of antenatal steroids on resting cortisol at any age. This result was not altered after adjusting for gestational age at birth, neonatal cumulative pain, morphine exposure, mechanical ventilation days and postnatal steroid exposure. Conclusions:  No effect of a single course of dexamethasone on resting salivary cortisol, an indicator of hypothalamic-pituitary-adrenal axis function, was found in infancy up to 18 months corrected age in infants born very preterm. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.

Effects of Genetic Variation in the P2RX7 Gene on Pharmacodynamics of a P2X(7) Receptor Antagonist: a Prospective Genotyping Approach

British Journal of Clinical Pharmacology. Feb, 2012  |  Pubmed ID: 22295949

Aims:  To investigate the effects of two single nucleotide polymorphisms (SNPs) in the human P2X(7) receptor gene (P2RX7) - 1068G>A (A348T) and 1513A>C (E496A) - on P2X(7) receptor function, using a specific receptor antagonist (GSK1370319A) and prospective genetic stratification. Methods:  Lipopolysaccharide (LPS) and ATP-stimulated IL-1β production was determined in the presence or absence of GSK1370319A in blood culture from 32 prospectively genotyped subjects. Results:  There was approximately 6.7 fold difference (p<0.0001) in IC(50) for inhibition of ATP-stimulated IL-1β release by GSK1370319A between individuals with the homozygous gain (1068A) and loss (1513C) of function genotypes (expressing the 348T, 496E and 348A, 496A alleles, respectively). Conclusions:  Leukocyte P2X(7) receptors had significantly altered pharmacodynamic responses to a specific antagonist (GSK1370319A), directly related to SNP genotype. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Expression of Inhibin/Activin Proteins and Receptors in the Human Hypothalamus and Basal Forebrain

Journal of Neuroendocrinology. Feb, 2012  |  Pubmed ID: 22296042

The inhibin/activin family of proteins is known to have a broad distribution of synthesis and expression in many species, and a variety of functions in reproductive and other physiological systems. Yet, our knowledge regarding the production and function of inhibin and activin in the central nervous system is relatively limited, especially in humans. Our objective was to explore the distribution of inhibin/activin protein subunits and receptors in the adult human brain. The human hypothalamus and surrounding basal forebrain was examined using post-mortem tissues from 29 adults. Immunocytochemical studies were conducted with antibodies directed against the inhibin/activin α, βA, and βB subunits, betaglycan and the activin type IIA and IIB receptors. Immunoassay was also utilised to measure dimeric inhibin A and B levels in tissue homogenates of the infundibulum of the hypothalamus. Robust βA subunit immunoreactivity was present in the paraventricular, supraoptic, lateral hypothalamic, infundibular, dorsomedial, and suprachiasmatic nuclei of the hypothalamus, in the basal ganglia, and in the nucleus basalis of Meynert. A similar staining distribution was noted for the βB subunit, betaglycan and the type II receptor antibodies, while α subunit staining was not detected in any of the major anatomical regions of the human brain. Inhibin B immunoreactivity was present in all tissues, while inhibin A levels were below detectable limits. These studies show for the first time that the inhibin/activin protein subunits and receptors can be co-localised in the human brain, implicating potential, diverse neural functions.

Laparoscopic Adrenalectomy for Phaeochromocytoma in a Twin Gestation

Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. Feb, 2012  |  Pubmed ID: 22296435

Gastrin-releasing Peptide Receptor Expression in Non-cancerous Bronchial Epithelia is Associated with Lung Cancer: a Case-control Study

Respiratory Research. Feb, 2012  |  Pubmed ID: 22296774

ABSTRACT: BACKGROUND: Normal bronchial tissue expression of GRPR, which encodes the gastrin-releasing peptide receptor, has been previously reported by us to be associated with lung cancer risk in 78 subjects, especially in females. We sought to define the contribution of GRPR expression in bronchial epithelia to lung cancer risk in a larger case-control study where adjustments could be made for tobacco exposure and sex. METHODS: We evaluated GRPR mRNA levels in histologically normal bronchial epithelial cells from 224 lung cancer patients and 107 surgical cancer-free controls. Associations with lung cancer were tested using logistic regression models. RESULTS: Bronchial GRPR expression was significantly associated with lung cancer (OR=4.76; 95% CI=2.32-9.77) in a multivariable logistic regression (MLR) model adjusted for age, sex, smoking status and pulmonary function. MLR analysis stratified by smoking status indicated that ORs were higher in never and former smokers (OR=7.74; 95% CI=2.96-20.25) compared to active smokers (OR=1.69; 95% CI=0.46-6.33). GRPR expression did not differ by subject sex, and lung cancer risk associated with GRPR expression was not modified by sex. CONCLUSIONS: GRPR expression in non-cancerous bronchial epithelium was significantly associated with the presence of lung cancer in never and former smokers. The association in never and former smokers was found in males and females. Association with lung cancer did not differ by sex in any smoking group.

Pacific Region Influenza Surveillance for Oseltamivir Resistance

Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. Jan, 2012  |  Pubmed ID: 22296793

BACKGROUND: Hawaii and the United States-affiliated Pacific islands (USAPI) host over 8 million travelers annually, most of whom originate in Asia, Australia, and the Americas where prevalence of oseltamivir resistance in 2009 pandemic influenza A (H1N1) has been reported to be 2.5-3.5%. OBJECTIVE: To survey a collection of samples from Hawaii and the USAPI that had tested positive for the 2009 pandemic influenza A (H1N1) virus by RTI-PCR to assess whether antiviral resistance emerged in these island communities during the 2009 H1N1 pandemic. STUDY DESIGN: We examined RNA extracted from Hawaiian and USAPI cases for the neuraminidase H275Y mutation associated with oseltamivir resistance by pyrosequencing. RESULTS: Two hundred and sixty-three (263) 2009 pandemic influenza A (H1N1) positive specimens were tested and 263/263 (100%) were shown to lack the mutation most commonly associated with oseltamivir resistance. CONCLUSIONS: There was no evidence of oseltamivir resistant A(H1N1)pdm09 virus during the 2009 pandemic in the Pacific islands despite considerable travel exposure. Geographic isolation, the lack of a "second wave" of pandemic influenza, judicious antiviral use, aggressive vaccination, and below average tourism due to the global economic crisis may have been contributing factors. Continued surveillance and vigilance is necessary to monitor unpredictable influenza activity.

[(11)C]GSK2126458 and [(18)F]GSK2126458, the First Radiosynthesis of New Potential PET Agents for Imaging of PI3K and MTOR in Cancers

Bioorganic & Medicinal Chemistry Letters. Feb, 2012  |  Pubmed ID: 22297110

GSK2126458 is a highly potent inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) with low picomolar to subnanomolar activity. [(11)C]GSK2126458 and [(18)F]GSK2126458, new potential PET agents for imaging of PI3K and mTOR in cancer, were first designed and synthesized in 40-50% and 20-30% decay corrected radiochemical yield, and 370-740 and 37-222GBq/μmol specific activity at end of bombardment (EOB), respectively.

Training Children with ADHD to Minimize Impulsivity in Auditory Contralateral Masking

International Journal of Pediatric Otorhinolaryngology. Jan, 2012  |  Pubmed ID: 22297209

OBJECTIVE: Impulsivity and distractibility are among the important symptoms of attention deficit hyperactivity disorder (ADHD). In this study, impulsivity is operationally measured using false-alarm rates in an auditory, contralateral-masking task. Intensive auditory training was attempted to decrease false alarm rates. METHODS: In contralateral masking there is a distracting noise in one ear on every trial and a threshold-level tone in the other ear on half of those trials. Participants indicated whether the tone was present or not and received immediate feedback. The intensity of the masked tone was adaptively varied to track threshold. False alarms are the error of commission, saying that a stimulus is present when it is not. Seven school-aged children with ADHD (ages 10-16) and four adults without ADHD were trained on this task for 900 trials per day over four consecutive days. RESULTS: False alarms from the children with ADHD decreased over the four days of training, beginning at the high level and ending at the low level expected from previous studies. There was no generalization to a different masking task. Results from the four adults were unexpected: soon after the training began they behaved no differently than the children with ADHD. CONCLUSION: Children with ADHD can be trained to become less impulsive in an auditory detection task.

Moderating Role of the MAOA Genotype in Antisocial Behaviour

The British Journal of Psychiatry : the Journal of Mental Science. Feb, 2012  |  Pubmed ID: 22297589

Recent studies have examined gene×environment (G×E) interactions involving the monoamine oxidase A (MAOA) gene in moderating the associations between exposure to adversity and antisocial behaviour. The present study examined a novel method for assessing interactions between a single gene and multiple risk factors related to environmental and personal adversity.

ANATOMICAL AND VISUAL RESULTS OF TRANSCONJUNCTIVAL SUTURELES VITRECTOMY USING SUBCONJUNCTIVAL ANESTHESIA PERFORMED ON SELECT PATIENTS TAKING ANTICOAGULANT AND ANTIPLATELET AGENTS

Retina (Philadelphia, Pa.). Jan, 2012  |  Pubmed ID: 22298013

PURPOSE: The purpose of this study was to report the observed outcomes of anticoagulated patients undergoing transconjunctival sutureless vitrectomies using subconjunctival anesthesia without preoperative cessation of anticoagulation and antiplatelet (AC/AP) agents. METHODS: A retrospective chart review was performed on patients taking AC/AP agents who were undergoing transconjunctival sutureless vitrectomies with subconjunctival anesthesia between January 2007 and June 2009. Intra- and postoperative complications (such as massive hemorrhage), anatomical results, satisfactory analgesia (informed by patients and recorded by surgeon), anatomical results, and visual acuity were documented. RESULTS: Sixty-three surgeries were performed on 56 eyes of 52 patients. Thirty-two patients were taking aspirin and clopidogrel, 18 were taking warfarin, 5 were taking clopidogrel, 3 were taking aspirin and warfarin, 2 were taking acetylsalicylic acid and dipyridamole, and 1 was taking warfarin and clopidogrel. All patients had satisfactory analgesia. No intraoperative complications occurred. Seven eyes (13%) had postoperative vitreous hemorrhage. Overall, 79% of patients had improved postoperative visual acuity, 16% of patients had unchanged visual acuity, and 5% of patients had worse visual acuity at last follow-up visit. CONCLUSION: Medical disease requiring systemic AC/AP therapy is often present in patients with vitreoretinal disease. Transconjunctival sutureless vitrectomies using subconjunctival anesthesia may be a safe and effective surgical option in select patients in whom cessation of AC/AP and/or delayed ophthalmic intervention is imprudent.

The Prevalence of Defensive Orthopaedic Imaging: a Prospective Practice Audit in Pennsylvania

The Journal of Bone and Joint Surgery. American Volume. Feb, 2012  |  Pubmed ID: 22298064

Defensive medicine has been identified as an area of wasteful health-care spending. Estimates of its prevalence and its contribution to the cost of defensive practices have varied widely. To date, there has been no prospective evaluation of the use of defensive medicine for musculoskeletal conditions.

Dynamic Mapping of CN Rotation Following Photoexcitation of ICN(-)

Angewandte Chemie (International Ed. in English). Feb, 2012  |  Pubmed ID: 22298354

In a spin: The dynamics of photoexcited ICN(-) (Ar)(0-5) are presented. Photodetachment produces quasi-thermal electron emission that leaves ICN with up to 2.85 eV of internal energy. Photodissociation at 2.5 eV leads to one-atom caging and highly solvated anion products. Calculations indicate efficient energy transfer into CN rotation upon excitation to the (2) Π(1/2) excited state. CN rotation is vital to explain the unique dynamics observed.

Developing a Millifluidic Platform for the Synthesis of Ultrasmall Nanoclusters: Ultrasmall Copper Nanoclusters As a Case Study

Small (Weinheim an Der Bergstrasse, Germany). Feb, 2012  |  Pubmed ID: 22298499

The future of lab-on-a-chip devices for the synthesis of nanomaterials hinges on the successful development of high-throughput methods with better control over their size. While significant effort in this direction mainly focuses on developing "difficult to fabricate" complex microfluidic reactors, scant attention has been paid to the "easy to fabricate" and simple millifluidic systems that could provide the required control as well as high throughput. By utilizing numerical simulation of fluids within the millifluidic space at different flow rates, the results presented here show velocity profiles and residence time distributions similar to the case of microfluidics. By significantly reducing the residence time and residence time distribution, a continuous flow synthesis of ultrasmall copper nanoclusters (UCNCs) with exceptional colloidal stability is achieved. In-situ synchrotron-radiation-based X-ray absorption spectroscopy (XAS) reveal that the as-prepared clusters are about 1 nm, which is further supported by transmission electron microscopy and UV-vis spectroscopy studies. The clusters reported here are the smallest ever produced using a lab-on-a-chip platform. When supported on silica, they are found to efficiently catalyze C-H oxidation reactions, hitherto unknown to be catalyzed by Cu. This work suggests that a millifluidic platform can be an inexpensive, versatile, easy-to-use, and powerful tool for nanoparticle synthesis in general, and more specifically for ultrasmall nanoclusters (UNCs).

A System for Coreference Resolution for the Clinical Narrative

Journal of the American Medical Informatics Association : JAMIA. Jan, 2012  |  Pubmed ID: 22298565

ObjectiveTo research computational methods for coreference resolution in the clinical narrative and build a system implementing the best methods.MethodsThe Ontology Development and Information Extraction corpus annotated for coreference relations consists of 7214 coreferential markables, forming 5992 pairs and 1304 chains. We trained classifiers with semantic, syntactic, and surface features pruned by feature selection. For the three system components-for the resolution of relative pronouns, personal pronouns, and noun phrases-we experimented with support vector machines with linear and radial basis function (RBF) kernels, decision trees, and perceptrons. Evaluation of algorithms and varied feature sets was performed using standard metrics.ResultsThe best performing combination is support vector machines with an RBF kernel and all features (MUC score=0.352, B(3)=0.690, CEAF=0.486, BLANC=0.596) outperforming a traditional decision tree baseline.DiscussionThe application showed good performance similar to performance on general English text. The main error source was sentence distances exceeding a window of 10 sentences between markables. A possible solution to this problem is hinted at by the fact that coreferent markables sometimes occurred in predictable (although distant) note sections. Another system limitation is failure to fully utilize synonymy and ontological knowledge. Future work will investigate additional ways to incorporate syntactic features into the coreference problem.ConclusionWe investigated computational methods for coreference resolution in the clinical narrative. The best methods are released as modules of the open source Clinical Text Analysis and Knowledge Extraction System and Ontology Development and Information Extraction platforms.

Oral Tocotrienols Are Transported to Human Tissues and Delay the Progression of the Model for End-Stage Liver Disease Score in Patients

The Journal of Nutrition. Feb, 2012  |  Pubmed ID: 22298568

The natural vitamin E family is composed of 8 members equally divided into 2 classes: tocopherols (TCP) and tocotrienols (TE). A growing body of evidence suggests TE possess potent biological activity not shared by TCP. The primary objective of this work was to determine the concentrations of TE (200 mg mixed TE, b.i.d.) and TCP [200 mg α-TCP, b.i.d.)] in vital tissues and organs of adult humans receiving oral supplementation. Eighty human participants were studied. Skin and blood vitamin E concentrations were determined from healthy participants following 12 wk of oral supplementation of TE or TCP. Vital organ vitamin E levels were determined by HPLC in adipose, brain, cardiac muscle, and liver of surgical patients following oral TE or TCP supplementation (mean duration, 20 wk; range, 1-96 wk). Oral supplementation of TE significantly increased the TE tissue concentrations in blood, skin, adipose, brain, cardiac muscle, and liver over time. α-TE was delivered to human brain at a concentration reported to be neuroprotective in experimental models of stroke. In prospective liver transplantation patients, oral TE lowered the Model for end-stage liver disease (MELD) score in 50% of patients supplemented, whereas only 20% of TCP-supplemented patients demonstrated a reduction in MELD score. This work provides, to our knowledge, the first evidence demonstrating that orally supplemented TE are transported to vital organs of adult humans. The findings of this study, in the context of the current literature, lay the foundation for Phase II clinical trials testing the efficacy of TE against stroke and end-stage liver disease in humans.

Intravitreal Dexamethasone in the Management of Delayed-onset Bleb-associated Endophthalmitis

International Journal of Inflammation. 2012  |  Pubmed ID: 22288020

Purpose. To report the visual acuity (VA) outcomes and culture results of delayed-onset bleb-associated endophthalmitis (BAE) with and without intravitreal dexamethasone (IVD). Methods. Retrospective nonrandomized comparative case series of BAE at Bascom Palmer Eye Institute between January 1, 1996 and December 31, 2009. Clinical data were compared using the 2-sided Student's t-test for patients who received IVD and patients who did not receive IVD. Results. 70/83 (84%) received IVD, and 13/83 (16%) did not receive IVD. Mean baseline VA was 20/90 in the IVD group and 20/70 in the group that did not receive IVD (P = 0.57). Mean presenting VA was 0.9/200 in the IVD group and 1.7/200 in the group that did not receive IVD (P = 0.23). Repeat cultures were positive in 2/70 (3%) IVD cases and 1/13 (8%) cases that did not receive IVD (P = 0.57). Mean VA at 1 month was 5/200 in the IVD group and 1.8/200 in the group that did not receive IVD, logMARΔ of 0.85 and 1.56, respectively (P = 0.02). Mean VA at 3 months was 7/200 in the IVD group and 3/200 in the group that did not receive IVD, logMARΔ of 0.74 and 1.33, respectively (P = 0.14). Conclusion. In the current study of BAE, IVD was associated with improved short-term VA outcomes without an increased rate of persistent infection.

INR Targets and Site-Level Anticoagulation Control: Results from the Veterans AffaiRs Study to Improve Anticoagulation (VARIA)

Journal of Thrombosis and Haemostasis : JTH. Jan, 2012  |  Pubmed ID: 22288563

Background: Not all clinicians target the same International Normalized Ratio (INR) for patients with a guideline-recommended target range of 2 to 3. A patient's mean INR value suggests the INR that was actually targeted. We hypothesized that sites would vary by mean INR, and that sites of care with mean values nearest to 2.5 would achieve better anticoagulation control, as measured by percent time in therapeutic range (TTR). Objectives: To examine variations among sites in mean INR and the relationship with anticoagulation control in an integrated system of care. Patients/Methods: We studied 103,897 patients receiving oral anticoagulation with an expected INR target between 2 and 3 at 100 Veterans Health Administration (VA) sites from 10/1/06-9/30/08. Key site-level variables were: proportion near 2.5 (that is, percent of patients with mean INR between 2.3-2.7) and mean risk-adjusted TTR. Results: Site mean INR ranged from 2.22-2.89; proportion near 2.5, from 30-64%. Sites' proportions of patients near 2.5, below 2.3, and above 2.7 were consistent from year to year. A 10 percentage point increase in the proportion near 2.5 predicted a 3.8 percentage point increase in risk-adjusted TTR (p < 0.001). Conclusions: Proportion of patients with mean INR near 2.5 is a site-level "signature" of care and an implicit measure of targeted INR. This proportion varies by site and is strongly associated with site-level TTR. Our study suggests that sites wishing to improve TTR, and thereby improve patient outcomes, should avoid the explicit or implicit pursuit of non-standard INR targets.

Inhibitory Effects on Response Force in the Stop-signal Paradigm

Journal of Experimental Psychology. Human Perception and Performance. Jan, 2012  |  Pubmed ID: 22288696

The forcefulness of key press responses was measured in stop-all and selective stopping versions of the stop-signal paradigm. When stop signals were presented too late for participants to succeed in stopping their responses, response force was nonetheless reduced relative to trials in which no stop signal was presented. This effect shows that peripheral motor aspects of primary task responses can still be influenced by inhibition even when the stop signal arrives too late to prevent the response. It thus requires modification of race models in which responses in the presence of stop signals are either stopped completely or produced normally, depending on whether the responding or stopping process finishes first. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Multicenter Study of Predictors of Suicide Screening in Emergency Departments

Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. Feb, 2012  |  Pubmed ID: 22288721

Objectives:  The objective was to provide estimates and predictors of screening for suicide in emergency departments (EDs). Methods:  Eight geographically diverse U.S. EDs each performed chart reviews of 100 randomly selected patients, ages 18 years or older, with visits in October 2009. Trained chart abstractors collected information on patient demographics, presentation, discharge diagnosis, suicide screening, and other mental health indicators. Univariate logistic regression was used to determine factors associated with suicide screening. Results:  The cohort of 800 patients had a median age of 41 years (interquartile range = 27 to 53 years) with 57% female, 16% Hispanic, 58% white, 23% black or African American, and 10% other race. Suicide screenings were documented for 39 patients (4.9%; 95% confidence interval [CI] = 3.4% to 6.4%). Of those screened, 23 (2.9% of total sample; 95% CI = 1.7% to 4.0%) were positive for suicidal ideation or behavior. Approximately 90% of those screened had documented complaints of a psychiatric nature at triage. About one-third had either documentation of alcohol abuse (33%) or intentional illegal or prescription drug misuse (36%). Conclusions:  The presence of known psychiatric problems and substance use had the strongest associations with suicide screening, yet even patients presenting with these indicators were not screened for suicide. Understanding factors that currently influence suicide screening in the ED will guide the design and implementation of improved suicide screening protocols and related interventions. ACADEMIC EMERGENCY MEDICINE 2012; 1-5 © 2012 by the Society for Academic Emergency Medicine.

Nevus/Melanocytoma/Melanoma? Nosologic Chaos

Archives of Pathology & Laboratory Medicine. Feb, 2012  |  Pubmed ID: 22288954

Continuous Thrombin Infusion Leads to a Bleeding Phenotype in Sheep

Thrombosis Research. Jan, 2012  |  Pubmed ID: 22289207

BACKGROUND: In addition to a recognized role in the coagulation cascade and haemostasis, thrombin is known to have multiple functions. We aimed to establish an ovine model to study thrombin effects in vivo. METHODS: Thrombin (0.0004-0.42IU/kg/min) was continuously infused in Austrian Mountain Sheep over five hours in the dose escalation study (n=5 animals; 15 experiments). In the dose verification study animals received 0.42IU/kg/min of thrombin vs. saline solution in a cross-over design (n=3 animals; 7 experiments). RESULTS: Thrombin at an infusion rate of 0.42IU/kg/min decreased fibrinogen levels by 75% (p<0.001) and increased degradation products of the fibrinogen beta-chain as shown in a proteomic analysis. Thrombin decreased platelet counts by 36% (p=0.006), prolonged thrombin time by 70% (p=0.012) and activated partial thromboplastin time by 32%. Interestingly, thrombin infusion significantly increased the activity of coagulation factors V and X (p<0.05) and decreased the activity of the coagulation factors VIII and XIII (p<0.05). Accordingly, thrombin displayed predominantly anti-coagulant and anti-platelet effects: 1) thrombin prolonged clotting time/clot formation time 7-fold (p=0.019) and induced a 65% decrease in maximal clot firmness (p<0.001); 2) thrombin reduced collagen- induced platelet aggregation by 85% and prolonged collagen/adenosine diphosphate closure time 3-fold; and 3) thrombin caused lung haemorrhage but not thromboembolism. CONCLUSION: Protracted intravenous infusion of thrombin over a period of five hours offers a new experimental model to study thrombin effects in a large animal species.

Predictors of Functional Outcome Change 18 Months After Anterior Ulnar Nerve Transposition

Archives of Physical Medicine and Rehabilitation. Feb, 2012  |  Pubmed ID: 22289242

Shi Q, MacDermid J, Grewal R, King GJ, Faber K, Miller TA. Predictors of functional outcome change 18 months after anterior ulnar nerve transposition.

Time-resolved Luminescence Resonance Energy Transfer Imaging of Protein-protein Interactions in Living Cells

Methods in Enzymology. 2012  |  Pubmed ID: 22289461

Lanthanide-based or luminescence resonance energy transfer (LRET) microscopy can be used to sensitively image interactions between reporter-labeled proteins in living mammalian cells. With LRET, luminescent lanthanide complexes are used as donors, conventional fluorophores are used as acceptors, and donor-sensitized acceptor emission occurs at time scales that reflect the long (∼ms) lanthanide emission lifetime. These long-lived signals can be separated from short-lifetime (∼ns) sample autofluorescence and directly excited acceptor fluorescence by using pulsed light to excite the specimen and by implementing a short delay (>100ns) before detection, thereby increasing measurement sensitivity. As practical implementation of time-resolved LRET microscopy requires several potentially unfamiliar experimental techniques, we explicitly describe herein methods to label proteins in living mammalian cells with luminescent terbium complexes, image interactions between terbium-labeled proteins and green fluorescent protein fusions, and quantitatively analyze LRET images.

Use of Traceback Methods To Confirm the Source of a Multistate Escherichia Coli O157:H7 Outbreak Due to In-Shell Hazelnuts

Journal of Food Protection. Feb, 2012  |  Pubmed ID: 22289593

Traceback methods by state regulatory agencies were used to complement traditional epidemiological cluster investigation methods and confirmed hazelnuts (also referred to as filberts) as the vehicle in a multistate outbreak of Escherichia coli O157:H7 infections. Bulk in-shell hazelnut and mixed-nut purchase locations were identified during the initial epidemiological interviews. Based on purchase dates and case onset dates, regulators in Minnesota, Michigan, and Wisconsin traced product back through the supply chain. Six (86%) retail locations received the suspect hazelnut or mixed-nut shipments from a Minnesota distributor, with one retailer (14%) receiving products from a Wisconsin distributor. Both distributors received 100% of their bulk in-shell hazelnuts and mixed nuts from a distributor in California. The California distributor received 99% of their hazelnuts from a packing company in Oregon. The California distributor received the hazelnuts in 50-lb (22.7-kg) bags and either resold them without opening the bags or used the in-shell hazelnuts in the manufacture of their in-shell mixed nuts. Records at the packing company in Oregon were incomplete or lacked sufficient detail needed to identify a suspect farm or group of suspect farms. Laboratory samples collected from human cases and subsequently recalled product matched the outbreak pulsed-field gel electrophoresis subtype of E. coli O157:H7. Hazelnut harvesting practices create a plausible route of contamination from fecal matter from domestic ruminants or wild deer. This outbreak investigation demonstrates the use of product traceback data to rapidly test an epidemiological hypothesis.

The Evolutionary Significance of Depression in Pathogen Host Defense (PATHOS-D)

Molecular Psychiatry. Jan, 2012  |  Pubmed ID: 22290120

Given the manifold ways that depression impairs Darwinian fitness, the persistence in the human genome of risk alleles for the disorder remains a much debated mystery. Evolutionary theories that view depressive symptoms as adaptive fail to provide parsimonious explanations for why even mild depressive symptoms impair fitness-relevant social functioning, whereas theories that suggest that depression is maladaptive fail to account for the high prevalence of depression risk alleles in human populations. These limitations warrant novel explanations for the origin and persistence of depression risk alleles. Accordingly, studies on risk alleles for depression were identified using PubMed and Ovid MEDLINE to examine data supporting the hypothesis that risk alleles for depression originated and have been retained in the human genome because these alleles promote pathogen host defense, which includes an integrated suite of immunological and behavioral responses to infection. Depression risk alleles identified by both candidate gene and genome-wide association study (GWAS) methodologies were found to be regularly associated with immune responses to infection that were likely to enhance survival in the ancestral environment. Moreover, data support the role of specific depressive symptoms in pathogen host defense including hyperthermia, reduced bodily iron stores, conservation/withdrawal behavior, hypervigilance and anorexia. By shifting the adaptive context of depression risk alleles from relations with conspecifics to relations with the microbial world, the Pathogen Host Defense (PATHOS-D) hypothesis provides a novel explanation for how depression can be nonadaptive in the social realm, whereas its risk alleles are nonetheless represented at prevalence rates that bespeak an adaptive function.Molecular Psychiatry advance online publication, 31 January 2012; doi:10.1038/mp.2012.2.

The Impact of Ordering Provider Specialty on Appropriateness Classification

Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology. Jan, 2012  |  Pubmed ID: 22290309

BACKGROUND: There is limited published data comparing the appropriateness use criteria for SPECT MPI with the specialty of the ordering provider. The aim of this study was to examine if the specialty of the ordering provider affected either the ordering indication or the appropriateness of stress SPECT MPI. METHODS AND RESULTS: The ordering provider's specialty was compared with the study indication and appropriateness rating. There were modest but significant differences in general indications by specialty. For example, the Emergency Department group ordered fewer studies in asymptomatic patients (3% compared to 14%-23% in the other four referral groups). In contrast, 43% of the studies ordered by Cardiovascular Division physicians and 39% of the studies ordered by the Registered Nurse group were on post-revascularization patients, compared to 23%-31% of those ordered by the other three groups. Overall appropriateness classification did not differ among the five specialty groups (P = 0.19). CONCLUSION: In a clinical practice where pre-operative testing using SPECT is infrequent, the rate of inappropriate studies was similar for all ordering providers. Quality improvement efforts in similar practices will likely require a broad educational focus on all ordering providers.

Synesthesia, Pseudo-Synesthesia, and Irritable Bowel Syndrome

Digestive Diseases and Sciences. Jan, 2012  |  Pubmed ID: 22290344

BACKGROUND AND AIMS: Synesthesia is a sensory disorder where the stimulation of one sensory modality can lead to a reaction in another which would not usually be expected to respond; for instance, someone might see a color on hearing a word such as a day of the week. Disordered perception of sensory information also appears to contribute to the pathophysiology of irritable bowel syndrome (IBS). The purpose of this exploratory study was to ascertain whether these two conditions might be linked in any way. METHODS: Two hundred consecutive IBS outpatients were screened for synesthesia and compared with 200 matched healthy volunteers (controls). Positive responders were tested for two types of synesthesia (grapheme-color and music-color/shape) using a questionnaire which was repeated after 3 months to test for reproducibility. RESULTS: Of the 200 IBS outpatients screened, 26 (13%) patients and six (3%) controls claimed to be synesthetic (P < 0.001). Reproducibility was more variable in IBS patients than controls but despite this variability, 15 (7.5%) patients compared with 5 (2.5%) controls had greater than 75% consistency (P = 0.036), and 19 (9.5%) patients and 6 (3%) controls had greater than 50% consistency (P = 0.012). A reproducibility of less than 50% was observed in seven (3.5%) patients and no controls (0%) (P = 0.015), and these individuals were classified as having pseudo-synesthesia. CONCLUSION: IBS patients clearly differ from controls in terms of claiming to have synesthetic experiences. These results justify additional studies on the relationship between IBS and synesthesia to further understand the neural mechanisms underpinning these two conditions and to establish whether they may be linked.

Recall Termination in Free Recall

Memory & Cognition. Jan, 2012  |  Pubmed ID: 22290593

Although much is known about the dynamics of memory search in the free recall task, relatively little is known about the factors related to recall termination. Reanalyzing individual trial data from 14 prior studies (1,079 participants in 28,015 trials) and defining termination as occurring when a final response is followed by a long nonresponse interval, we observed that termination probability increased throughout the recall period and that retrieval was more likely to terminate following an error than following a correct response. Among errors, termination probability was higher following prior-list intrusions and repetitions than following extralist intrusions. To verify that this pattern of results can be seen in a single study, we report a new experiment in which 80 participants contributed recall data from a total of 9,122 trials. This experiment replicated the pattern observed in the aggregate analysis of the prior studies.

Intact Prototype Formation but Impaired Generalization in Autism

Research in Autism Spectrum Disorders. 2012  |  Pubmed ID: 22291857

Cognitive processing in autism has been characterized by a difficulty with the abstraction of information across multiple stimuli or situations and subsequent generalization to new stimuli or situations. This apparent difficulty leads to the suggestion that prototype formation, a process of creating a mental summary representation of multiple experienced stimuli that go together in a category, may be impaired in autism. Adults with high functioning autism and a typically developing comparison group matched on age and IQ completed a random dot pattern categorization task. Participants with autism demonstrated intact prototype formation in all four ways it was operationally defined, and this performance was not significantly different from that of control participants. However, participants with autism categorized dot patterns that were more highly distorted from the category prototypes less accurately than did control participants. These findings suggest, at least within the constraints of the random dot pattern task, that although prototype formation may not be impaired in autism, difficulties may exist with the generalization of what has been learned about a category to novel stimuli, particularly as they become less similar to the category's prototype.

Semi-automated Device for Batch Extraction of Metabolites from Tissue Samples

Analytical Chemistry. Jan, 2012  |  Pubmed ID: 22292466

Metabolomics has become a mainstream analytical strategy for investigating metabolism. The quality of data derived from these studies is proportional to the consistency of the sample preparation. Although considerable research has been devoted to finding optimal extraction protocols, most of the established methods require extensive sample handling. Manual sample preparation can be highly effective in the hands of skilled technicians, but an automated tool for purifying metabolites from complex biological tissues would be of obvious utility to the field. Here, we introduce the semi-automated metabolite batch extraction device (SAMBED), a new tool designed to simplify metabolomics sample preparation. We discuss SAMBED's design and show that SAMBED-based extractions are of comparable quality to extracts produced through traditional methods (11% average error from SAMBED versus 13% from manual extractions). Moreover, we show that aqueous SAMBED-based methods can be completed in less than a quarter of the time required for manual extractions.

Risk and Protective Factors Related to HIV-risk Behavior: A Comparison Between HIV-positive and HIV-negative Young Men Who Have Sex with Men

AIDS Care. Jan, 2012  |  Pubmed ID: 22292776

The objective of this study was to assess and compare the prevalence of high-risk sexual behaviors among young HIV-negative (n=8064) and HIV-positive (n=171) men who have sex with men (MSM) on predictors of unprotected anal intercourse (UAI). Using venue-based time-space sampling, 8235 MSM aged 15-25 were anonymously surveyed as a part of the Community Intervention Trial for Youth (CITY). The Project was conducted in 13 communities across the USA from 1999 to 2002. Forty percent of HIV-positive men and 34% of HIV-negative men reported that they had UAI in the previous 3 months. HIV-positive MSM were more likely than their uninfected peers to have traded sex within the previous year, to have had sex while high during their last sexual encounter, and to have UAI with a greater number of partners. Multivariate analyses indicated that for HIV-negative men, positive peer norms regarding safer sex and being Black or Latino predicted avoidance of UAI. Among HIV-positive men, having social support for safer sex and positive peer norms predicted avoidance of UAI. Young HIV-positive MSM are a relevant subgroup for prevention because they constitute a significant source from which future infections could be generated.

Metacridamides A and B, Macrocycles from Conidia of the Entomopathogenic Fungus Metarhizium Acridum

Journal of Natural Products. Jan, 2012  |  Pubmed ID: 22292922

Metarhizium acridum, an entomopathogenic fungus, has been commercialized and used successfully for biocontrol of grasshopper pests in Africa and Australia. Its conidia produce two novel 17-membered macrocycles, metacridamides A (1) and B (2), which consist of a Phe unit condensed with a nonaketide. Planar structures were elucidated by a combination of mass spectrometric and NMR techniques. Following hydrolysis of 1, chiral amino acid analysis assigned the l-configuration to the Phe unit. A crystal structure established the absolute configuration of the eight remaining stereogenic centers in 1. Metacridamide A (1) showed cytotoxicity to three cancer lines with IC(50)'s of 6.2, 11.0, and 10.8 μM against Caco-2 (epithelial colorectal adenocarcinoma), MCF-7 (breast cancer), and HepG2/C3A (hepatoma) cell lines, respectively. In addition, metacridamide B (2) had an IC(50) of 18.2 μM against HepG2/C3A, although it was inactive at 100 μM against Caco-2 and MCF-7. Neither analogue showed antimicrobial, phytotoxic, or insecticidal activity.

A Brief Mindfulness-based Cognitive Behavioral Intervention Improves Sexual Functioning Versus Wait-list Control in Women Treated for Gynecologic Cancer

Gynecologic Oncology. Jan, 2012  |  Pubmed ID: 22293042

GOAL: The goal of this study was to evaluate a mindfulness-based cognitive behavioral intervention for sexual dysfunction in gynecologic cancer survivors compared to a wait-list control group. METHODS: Thirty-one survivors of endometrial or cervical cancer (mean age 54.0, range 31-64) who self-reported significant and distressing sexual desire and/or sexual arousal concerns were assigned either to three, 90-minute mindfulness-based cognitive behavior therapy sessions or two months of wait-list control prior to entering the treatment arm. Validated measures of sexual response, sexual distress, and mood, as well as laboratory-evoked physiological and subjective sexual arousal were assessed at pre-, one month post-, and 6-months following treatment. RESULTS: There were no significant effects of the wait-list condition on any measure. Treatment led to significant improvements in all domains of sexual response, and a trend towards significance for reducing sexual distress. Perception of genital arousal during an erotic film was also significantly increased following the intervention despite no change in physiologically-measured sexual arousal. CONCLUSIONS: A brief mindfulness-based intervention was effective for improving sexual functioning. Geographic restrictions permitted only a select sample of survivors to participate, thus, the generalizability of the findings is limited. Future studies should aim to develop online modalities for treatment administration to overcome this limitation.

Nurse Staffing Legislation: an Overview

The Journal of Perinatal & Neonatal Nursing. Jan, 2012  |  Pubmed ID: 22293636

A New Year's Resolution

The Journal of Perinatal & Neonatal Nursing. Jan, 2012  |  Pubmed ID: 22293648

Policy: Adaptations of Avian Flu Virus Are a Cause for Concern

Nature. Feb, 2012  |  Pubmed ID: 22294204

Effect of Hydroxyurea Treatment on Renal Function Parameters: Results from the Multi-center Placebo-controlled Baby Hug Clinical Trial for Infants with Sickle Cell Anemia

Pediatric Blood & Cancer. Jan, 2012  |  Pubmed ID: 22294512

BACKGROUND: Children with sickle cell anemia (SCA) often develop hyposthenuria and renal hyperfiltration at an early age, possibly contributing to the glomerular injury and renal insufficiency commonly seen later in life. The Phase III randomized double-blinded Clinical Trial of Hydroxyurea in Infants with SCA (BABY HUG) tested the hypothesis that hydroxyurea can prevent kidney dysfunction by reducing hyperfiltration. PROCEDURE: 193 infants with SCA (mean age 13.8 months) received hydroxyurea 20 mg/kg/day or placebo for 24 months. (99m) Tc diethylenetriaminepentaacetic acid (DTPA) clearance, serum creatinine, serum cystatin C, urinalysis, serum and urine osmolality after parent-supervised fluid deprivation, and renal ultrasonography were obtained at baseline and at exit to measure treatment effects on renal function. RESULTS: At exit children treated with hydroxyurea had significantly higher urine osmolality (mean 495 mOsm/kg H(2) O compared to 452 in the placebo group, P = 0.007) and a larger percentage of subjects taking hydroxyurea achieved urine osmolality >500 mOsm/kg H(2) O. Moreover, children treated with hydroxyurea had smaller renal volumes (P = 0.007). DTPA-derived glomerular filtration rate (GFR) was not significantly different between the two treatment groups, but was significantly higher than published norms. GFR estimated by the Chronic Kidney Disease in Children (CKiD) Schwartz formula was the best non-invasive method to estimate GFR in these children, as it was the closest to the DTPA-derived GFR. CONCLUSION: Treatment with hydroxyurea for 24 months did not influence GFR in young children with SCA. However, hydroxyurea was associated with better urine concentrating ability and less renal enlargement, suggesting some benefit to renal function. (ClinicalTrials.gov number NCT00006400) Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc.

Investigating the Effectiveness of St John's Wort Herb As an Antimicrobial Agent Against Mycobacteria

Phytotherapy Research : PTR. Feb, 2012  |  Pubmed ID: 22294548

A persistent need exists for effective treatment agents for mycobacterial infections. This research investigated the effectiveness of the Hypericum perforatum herb (commonly known as St John's wort; SJW) in its growth inhibition of mycobacteria. A SJW extract was effective at inhibiting five nonpathogenic Mycobacterium isolates and Bacillus subtilis, but not Escherichia coli. Quantitative studies of concentration sensitivity to the SJW extract were performed with minimal bactericidal concentrations (MBC) ranging from 0.33 to 2.66 mg extract/mL. The SJW compounds hyperforin (Hfn), hypericin (Hpn), and pseudohypericin (Phn) were quantified in the extract using HPLC. The SJW extract solution of 133 mg extract/mL used in this study contained 2.3 mg Hfn/mL, 0.8 mg Hpn/mL, and 2.1 mg Phn/mL. Purified Hfn, Hpn, and Phn were tested for inhibitory activity against Mycobacterium JLS (M. JLS) at similar concentrations used in the crude extract. While Hfn was inhibitory at 46 µg/mL, none of the purified SJW constituents were bactericidal at concentrations corresponding to SJW treatments. Scanning electron microscopy (SEM) analysis of SJW-treated M. JLS cells showed changes in cell surface morphology. Copyright © 2012 John Wiley & Sons, Ltd.

Public Health and Biosecurity. Adaptations of Avian Flu Virus Are a Cause for Concern

Science (New York, N.Y.). Feb, 2012  |  Pubmed ID: 22294736

Preclinical Characterization of a Novel Diphenyl Benzamide Selective ERα Agonist for Hormone Therapy in Prostate Cancer

Endocrinology. Jan, 2012  |  Pubmed ID: 22294742

Androgen deprivation therapy (ADT) is the mainstay of treatment for advanced prostate cancer. ADT improves overall and disease-free survival rates, but long-term therapy is associated with severe side effects of androgen and estrogen depletion including hot flashes, weight gain, depression, and osteoporosis. Effective hormone reduction can be achieved without estrogen deficiency-related side effects by using therapy with estrogenic compounds. However, cardiovascular complications induced by estrogens coupled with the availability of LHRH agonists led to discontinuation of estrogen use for primary androgen deprivation therapy in the 1980s. New treatments for prostate cancer that improve patient outcomes without the serious estrogen deficiency-related toxicities associated with ADT using LHRH analogs are needed. Herein we describe a novel nonsteroidal selective estrogen receptor-α agonist designed for first-line therapy of advanced prostate cancer that in animal models induces medical castration and minimizes many of the estrogen deficiency-related side effects of ADT. The present studies show that orally administered GTx-758 reversibly suppressed testosterone to castrate levels and subsequently reduced prostate volume and circulating prostate-specific antigen in relevant preclinical models without inducing hot flashes, bone loss, thrombophilia, hypercoagulation, or increasing fat mass.

A Closed Literature-based Discovery Technique Finds a Mechanistic Link Between Hypogonadism and Diminished Sleep Quality in Aging Men

Sleep. 2012  |  Pubmed ID: 22294819

Sleep quality commonly diminishes with age, and, further, aging men often exhibit a wider range of sleep pathologies than women. We used a freely available, web-based discovery technique (Semantic MEDLINE) supported by semantic relationships to automatically extract information from MEDLINE titles and abstracts.