Protocols and Video Articles Authored by Eloise Stapleton (Translated to Turkish)

The Hybrid Approach--current Knowns and Unknowns: the Perspective of Cardiology Cardiology in the Young. Dec, 2011 | Pubmed ID: 22152528 The hybrid approach to the treatment of patients with hypoplastic left heart syndrome most commonly includes transcatheter placement of a stent in the arterial duct and surgical placement of bands on the branch pulmonary arteries via median sternotomy. This manuscript will review the concept of hybrid palliation and discuss topics related to several time intervals: peri-procedural, post-procedural, interstage, and comprehensive stage 2.

Late Catheter Interventions in Hypoplastic Left Heart Syndrome Cardiology in the Young. Dec, 2011 | Pubmed ID: 22152531 Interventional cardiology plays a key role in the diagnosis and management of patients with functionally univentricular physiology after the various stages of surgical palliation. The interventions performed are widely variable in type, including angioplasty of stenotic vessels and implantation of stents in stenotic vessels; closure of defects such as collaterals, leaks in baffles, and fenestrations; creation of fenestration; and more. In the setting of venous hypertension associated with stenosis at the Fontan baffle, conduit, or pulmonary arteries, stent implantation is often preferred, as the aim is to eliminate completely the narrowing, given that relatively mild stenosis can have a significant detrimental hemodynamic effect in patients with functionally univentricular circulation. The procedure is highly successful. In patients who fail after Fontan procedure, creation of a fenestration is often performed, with variable technique depending on the underlying anatomic substrate. To increase chances of patency of the fenestration, implantation of a stent is often required, particularly in the setting of an extracardiac conduit. For those patients with cyanosis and favorable Fontan hemodynamics, closure of the fenestration is performed using atrial septal occluder devices with high success rate. Coils compatible with magnetic resonance imaging are used widely to treat collateral vessels, although on occasion other specific embolization tools are required, such as particles or vascular plugs. Postoperative arch obstruction is successfully managed with angioplasty at a younger age, while implantation of a stent in the aorta is reserved for older patients. Specifics of these interventional procedures as applied to the population of patients with functionally univentricular hearts are described in this manuscript.

Long-term Management of Patients with Hypoplastic Left Heart Syndrome: the Diagnostic Approach at All Children's Hospital Cardiology in the Young. Dec, 2011 | Pubmed ID: 22152533 Improved survival in children with hypoplastic left heart syndrome has created a sub-population of children and young adults who are living with functionally univentricular physiology. Routine surveillance with comprehensive screening for structural cardiac disease, functional cardiac disease, arrhythmias, thromboembolic disease, and associated dysfunction of end organs is important. Future directives will better define the plans of care for routine surveillance in patients with hypoplastic left heart syndrome.

Competition for FcRn-mediated Transport Gives Rise to Short Half-life of Human IgG3 and Offers Therapeutic Potential Nature Communications. 2011 | Pubmed ID: 22186895 Human IgG3 displays the strongest effector functions of all IgG subclasses but has a short half-life for unresolved reasons. Here we show that IgG3 binds to IgG-salvage receptor (FcRn), but that FcRn-mediated transport and rescue of IgG3 is inhibited in the presence of IgG1 due to intracellular competition between IgG1 and IgG3. We reveal that this occurs because of a single amino acid difference at position 435, where IgG3 has an arginine instead of the histidine found in all other IgG subclasses. While the presence of R435 in IgG increases binding to FcRn at neutral pH, it decreases binding at acidic pH, affecting the rescue efficiency-but only in the presence of H435-IgG. Importantly, we show that in humans the half-life of the H435-containing IgG3 allotype is comparable to IgG1. H435-IgG3 also gave enhanced protection against a pneumococcal challenge in mice, demonstrating H435-IgG3 to be a candidate for monoclonal antibody therapies.

How Common is "parking" Among Social Security Disability Insurance Beneficiaries? Evidence from the 1999 Change in the Earnings Level of Substantial Gainful Activity Social Security Bulletin. 2011 | Pubmed ID: 22191286 Fewer Social Security Disability Insurance (DI) beneficiaries have their earnings suspended or terminated because of work than those who are actually working, partly because beneficiaries "park" earnings at a level below substantial gainful activity (SGA) to retain benefits. We assess the extent of parking by exploiting the 1999 change in the SGA earnings level from $500 to $700 monthly for nonblind beneficiaries using a difference-indifference analysis that compares two annual cohorts of beneficiaries who completed their trial work period, one that was affected by the SGA change and one that was not. Our impact estimates, along with results from other sources, suggest that from 0.2 to 0.4 percent of all DI beneficiaries were parked below the SGA level in the typical month from 2002 through 2006. The SGA change did not yield any difference in mean earnings, although it did result in a small reduction in months spent off of the rolls because of work.

Translating Sexual Assault Prevention from a College Campus to a United States Military Installation: Piloting the Know-your-power Bystander Social Marketing Campaign Journal of Interpersonal Violence. May, 2012 | Pubmed ID: 22080576 One population that shares both similar and different characteristics with traditional college-age students is the U.S. Military. Similarities include a high concentration of 18- to 26-year-olds dealing with new found independence, peer pressure, and the presence of social norms that support violence and hypermasculinity. Sexual violence is a major public health problem in the United States, and because of the similarities in the age group of college and military populations, the problems regarding sexual violence in both constituencies have been well-documented. In the current pilot study we seek to add to both current knowledge about and promising practices of translating prevention strategies from one target audience to another. We describe how we translated, administered, and evaluated a bystander intervention social marketing campaign focused on sexual assault prevention that had been found to significantly affect attitude change on a college campus for a U.S. Army installation in Europe. In addition to demonstrating the process of translating prevention strategies across target audiences, findings from this pilot study contribute to the evaluation data on the effectiveness of sexual violence prevention strategies implemented with members of the U.S. Military. From our analysis, we see that research participants indicate that the degree to which the images resonate with them and the familiarity of the context (i.e., social self-identification) significantly effect the participants' personal responsibility for reducing sexual assault, confidence in acting as a bystander, and reported engagement as a bystander.

Diffuse Central Neurocytoma with Craniospinal Dissemination Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. Jan, 2012 | Pubmed ID: 22088950 Central neurocytomas (CN) are benign central nervous system (CNS) tumors of neuroglial origin that represent 0.25 to 0.5% of all intracranial tumors in adults and an even smaller proportion of pediatric CNS tumors. These tumors characteristically occur in the subependymal layer of the lateral ventricle near the foramen of Monro and appear as sharply demarcated, solitary lesions. Surgical resection is considered curative, as the reported recurrence rate is less than 5% for patients with localized disease. In this report, we describe the case of a three-year-old boy with a diffuse CN with craniospinal dissemination identified at the time of diagnosis. Given the extensive nature of the disease, surgical resection was not indicated and he underwent a chemotherapeutic regimen of vincristine and carboplatin. At 18 months followup, the patient has completed 6 of 8 total cycles of vincristine and carboplatin and serial imaging shows stable disease within the craniospinal axis.

Out of Sight, out of Mind: Including Group Quarters Residents with Household Residents Can Change What We Know About Working-age People with Disabilities Demography. Feb, 2012 | Pubmed ID: 22109082 Information about residents of institutional and noninstitutional group quarters (GQ), particularly those with disabilities, has been limited by gaps in survey data, and statistics based on data that exclude some or all GQ residents are biased as estimates of total population statistics. We used the 2006 and 2007 American Community Survey (ACS) to identify the distribution of working-age populations with and without disabilities by major residence type and to assess the sensitivity of disability statistics to GQ residence. Our findings show that (1) of those with disabilities, about 1 in 13 males and 1 in 33 females live in GQ; (2) GQ rates are higher for individuals reporting mental, self-care, or go-outside-the-home disabilities than for those reporting sensory, physical, or employment disabilities; (3) younger males with disabilities are more likely to reside there, particularly at institutional GQ, reflecting their relatively high incarceration rate; (4) individuals with and without disabilities who are black, American Indian, were never married, or have less than a high school education have higher GQ residence rates; (5) 40% of male and 62% of female GQ residents have a disability; (6) adding GQ residents to household residents increases estimated disability prevalence for males by 6%, and the estimated difference between disability prevalence rates by gender nearly disappears; and (7) inclusion of the GQ population substantially lowers employment rate estimates for young males, blacks, and American Indians.

Conservative Versus Surgical Management of Idiopathic Normal Pressure Hydrocephalus: a Prospective Double-blind Randomized Controlled Trial: Study Protocol Acta Neurochirurgica. Supplement. 2012 | Pubmed ID: 22116416 There is no level I evidence to indicate whether placement of a shunt is effective in the management of idiopathic normal pressure hydrocephalus (INPH), because no trial has as yet compared the placement of a shunt versus no shunt in a randomized controlled manner. We started recruiting patients into a prospective double-blind randomized controlled study aiming to provide class I evidence supporting or refuting the role of surgical management in INPH. Inclusion criterion was the diagnosis of probable INPH plus objective improvement of walking speed following 72 h of extended lumbar drainage. Patients with concomitant Alzheimer's disease or vascular dementia were excluded. All patients included in the trial were to have a shunt placed with proGAV(Â®) adjustable valve. Patients were randomly assigned into two groups: group A was to have the shunt immediately adjusted to function, and group B was to have the shunt valve adjusted to the highest setting for 3 months then adjusted to function. Assessment of gait, cognitive function, and urinary symptoms were done before shunt insertion and at 3 months. Primary end point was to be an improvement in gait. Secondary end points were improvement in mental function or urinary function and incidence of complications. Final results are expected mid 2011.

Contact Lens-related Microbial Keratitis: How Have Epidemiology and Genetics Helped Us with Pathogenesis and Prophylaxis Eye (London, England). Feb, 2012 | Pubmed ID: 22134592 Contact lens wear is a common predisposing factor in microbial keratitis and is one of the two preventable risk factors for corneal infection in a working age population. Our understanding of the prevention and prophylaxis of contact lens-related corneal infection is informed by recent epidemiological studies describing the incidence of and risk factors for the disease, the effect of causative organism on disease severity, and an appreciation of individual immune profiles in susceptibility to and severity of the disease. Although contemporary contact lenses have not reduced the overall incidence of keratitis, a reduction in morbidity may be achievable through recognition of appropriate risk factors in severe disease, including avoiding delays in presenting for appropriate treatment, and attention to storage case hygiene practise. Severe keratitis is most commonly associated with an environmental causative organism, and daily disposable lenses are associated with less severe disease. Pseudomonas aeruginosa remains the commonest cause of contact lens-related corneal infection probably because of its unique virulence characteristics and ability to survive in the contact lens/storage case/ocular environment. In two recent outbreaks of contact lens-related infections, there has been a strong association demonstrated with particular contact lens solutions. Since the recall of these specific contact lens solutions, the rate of Acanthamoeba keratitis has remained above the expected baseline, indicating unidentified risk factors that may include environmental exposures. Individual differences in susceptibility to microbial keratitis may be partly explained by differences in single-nucleotide polymorphisms in certain cytokine genes, particularly those with a proven protective role in corneal infection.

Impact of Dust from Multiple Microenvironments and Diet on PentaBDE Body Burden Environmental Science & Technology. Jan, 2012 | Pubmed ID: 22142368 Our objectives were to determine relative contributions of diet and dust exposure from multiple microenvironments to PentaBDE body burden, and to explore the role of handwipes as a measure of personal exposure to PentaBDE. We administered a food frequency questionnaire and collected serum, dust (office, main living area, bedroom, and vehicle), and handwipe samples from 31 participants. Î£PentaBDEs (sum of BDE 28/33, 47, 99, 100, and 153) in handwipes collected in the office environment were weakly correlated with dust collected from offices (r = 0.35, p = 0.06) and bedrooms (r = 0.39, p = 0.04), but not with dust from main living areas (r = -0.05, p = 0.77) or vehicles (r = 0.17, p = 0.47). Î£PentaBDEs in serum were correlated with dust from main living areas (r = 0.42, p = 0.02) and bedrooms (r = 0.49, p = 0.008), but not with dust from offices (r = 0.22, p = 0.25) or vehicles (r = 0.20, p = 0.41). Our final regression model included variables for main living area dust and handwipes, and predicted 55% of the variation in serum Î£PentaBDE concentrations (p = 0.0004). Diet variables were not significant predictors of Î£PentaBDEs in serum. Our research suggests that exposure to dust in the home environment may be the most important factor in predicting PentaBDE body burden in North Americans, and potential exposure pathways may involve PBDE residues on hands.

Polyfluorinated Compounds in Serum Linked to Indoor Air in Office Environments Environmental Science & Technology. Jan, 2012 | Pubmed ID: 22148395 We aimed to investigate the role of indoor office air on exposure to polyfluorinated compounds (PFCs) among office workers. Week-long, active air sampling was conducted during the winter of 2009 in 31 offices in Boston, MA. Air samples were analyzed for fluorotelomer alcohols (FTOHs), sulfonamides (FOSAs), and sulfonamidoethanols (FOSEs). Serum was collected from each participant (n = 31) and analyzed for 12 PFCs including PFOA and PFOS. In air, FTOHs were present in the highest concentrations, particularly 8:2-FTOH (GM = 9920 pg/m(3)). FTOHs varied significantly by building with the highest levels observed in a newly constructed building. PFOA in serum was significantly correlated with air levels of 6:2-FTOH (r = 0.43), 8:2-FTOH (r = 0.60), and 10:2-FTOH (r = 0.62). Collectively, FTOHs in air significantly predicted PFOA in serum (p < 0.001) and explained approximately 36% of the variation in serum PFOA concentrations. PFOS in serum was not associated with air levels of FOSAs/FOSEs. In conclusion, FTOH concentrations in office air significantly predict serum PFOA concentrations in office workers. Variation in PFC air concentrations by building is likely due to differences in the number, type, and age of potential sources such as carpeting, furniture, and/or paint.

Efficacy Results of a Trial of a Herpes Simplex Vaccine The New England Journal of Medicine. Jan, 2012 | Pubmed ID: 22216840 Two previous studies of a herpes simplex virus type 2 (HSV-2) subunit vaccine containing glycoprotein D in HSV-discordant couples revealed 73% and 74% efficacy against genital disease in women who were negative for both HSV type 1 (HSV-1) and HSV-2 antibodies. Efficacy was not observed in men or HSV-1 seropositive women.

A Direct Method and ICER Tables for the Estimation of the Cost-effectiveness of Smoking Cessation Interventions in General Populations: Application to a New Cytisine Trial and Other Examples Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. Apr, 2012 | Pubmed ID: 22232061 The popularity of smoking cost-effectiveness (CE) analysis has grown rapidly. Differences in models and inputs mean results may not be comparable, and researchers may have to take them on trust because the methods are beyond their expertise and not always transparent. We describe a direct method and tables of results for researchers without specialist knowledge.

Experimental Pain Ratings and Reactivity of Cortisol and Soluble Tumor Necrosis Factor-Î± Receptor II Following a Trial of Hypnosis: Results of a Randomized Controlled Pilot Study Pain Medicine (Malden, Mass.). Jan, 2012 | Pubmed ID: 22233394 Current evidence supports the efficacy of hypnosis for reducing the pain associated with experimental stimulation and various acute and chronic conditions; however, the mechanisms explaining how hypnosis exerts its effects remain less clear. The hypothalamic-pituitary-adrenal (HPA) axis and pro-inflammatory cytokines represent potential targets for investigation given their purported roles in the perpetuation of painful conditions; yet, no clinical trials have thus far examined the influence of hypnosis on these mechanisms.

Physician and Dentist: New Initiatives to Jointly Mitigate Early Childhood Oral Disease Clinical Pediatrics. Feb, 2012 | Pubmed ID: 22267859

Exploring the Relationship Between Self-awareness of Driving Efficacy and That of a Proxy when Determining Fitness to Drive After Stroke Australian Occupational Therapy Journal. Feb, 2012 | Pubmed ID: 22272884 The inclusion of a driving specific self-awareness measure may assist the clinical screening process to determine fitness to drive after stroke. This article reports on the use of the Adelaide Driving Self-Efficacy Scale (ADSES) and a proxy ADSES for completion by a significant other in assessment of fitness to drive post-stroke.

Measurement of Flame Retardants and Triclosan in Municipal Sewage Sludge and Biosolids Environment International. Apr, 2012 | Pubmed ID: 22280921 As polybrominated diphenyl ethers (PBDEs) face increasing restrictions worldwide, several alternate flame retardants are expected to see increased use as replacement compounds in consumer products. Chemical analysis of biosolids collected from wastewater treatment plants (WWTPs) can help determine whether these flame retardants are migrating from the indoor environment to the outdoor environment, where little is known about their ultimate fate and effects. The objective of this study was to measure concentrations of a suite of flame retardants, and the antimicrobial compound triclosan, in opportunistic samples of municipal biosolids and the domestic sludge Standard Reference Material (SRM) 2781. Grab samples of biosolids were collected from two WWTPs in North Carolina and two in California. Biosolids samples were also obtained during three subsequent collection events at one of the North Carolina WWTPs to evaluate fluctuations in contaminant levels within a given facility over a period of three years. The biosolids and SRM 2781 were analyzed for PBDEs, hexabromobenzene (HBB), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (TBB), di(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), the chlorinated flame retardant Dechlorane Plus (syn- and anti-isomers), and the antimicrobial agent 5-chloro-2-(2,4-dichlorophenoxy)phenol (triclosan). PBDEs were detected in every sample analyzed, and Î£PBDE concentrations ranged from 1750 to 6358ng/g dry weight. Additionally, the PBDE replacement chemicals TBB and TBPH were detected at concentrations ranging from 120 to 3749 ng/g dry weight and from 206 to 1631 ng/g dry weight, respectively. Triclosan concentrations ranged from 490 to 13,866 ng/g dry weight. The detection of these contaminants of emerging concern in biosolids suggests that these chemicals have the potential to migrate out of consumer products and enter the outdoor environment.

Patterns of Drinking-related Protective and Risk Behaviors in College Student Drinkers Addictive Behaviors. Apr, 2012 | Pubmed ID: 22281283 Drinking-related protective (e.g., pacing consumption) and risk (e.g., participating in drinking games) behaviors influence both the amount of alcohol consumed and the consequences experienced by college students. Previous studies of these behaviors have typically examined use and predictors of these constructs separately. In the current study, latent profile analysis (LPA) was used to identify latent subgroups of drinkers with distinct patterns of use of both drinking-related protective and risk behaviors in a sample of college students. A random sample of first year student drinkers (N=229, 59.4% female) at a large, public university in the Northeastern United States completed a web-based assessment of drinking-related protective and risk behaviors, alcohol use, and related consequences. Three patterns of use were identified, including: 1) students who used protective behaviors frequently and seldom engaged in risk behaviors (10%), 2) students who used risk behaviors more frequently and used protective behaviors less often (30%), and 3) students who used both risk and protective behaviors at similar frequencies (60%). Significant differences in the distribution of profiles were observed when considering gender, age of onset of alcohol use, and recent drinking outcomes including weekend alcohol use, heavy-episodic drinking, and alcohol-related problems. Prevention and intervention programs may benefit from a focus on not only increasing protective actions, but on also reducing risk behaviors beyond that of quantity and frequency of alcohol use alone.

Corneal and Conjunctival Sensory Function: the Impact on Ocular Surface Sensitivity of Change from Low to High Oxygen Transmissibility Contact Lenses Investigative Ophthalmology & Visual Science. Mar, 2012 | Pubmed ID: 22281824 Deprivation of oxygen to the ocular surface during contact lens wear has been implicated in the alteration of sensory function. This study investigates whether increasing oxygen availability through discontinuation of contact lens wear or transfer into highly oxygen transmissible (high Dk/t) lenses leads to a change in corneal or conjunctival sensitivity.

In Vivo Assessment of Anti-microbial Efficacy of Silver-impregnated Contact Lens Storage Cases Investigative Ophthalmology & Visual Science. Feb, 2012 | Pubmed ID: 22297489 Purpose:To evaluate microbial contamination in silver-impregnated contact lens (CL) storage cases, while establishing the effect of 'wet' and 'dry' case maintenance and to determine its association with clinical signs, symptoms and compliance.Methods:Two non-contemporaneous prospective studies were conducted. Regular storage cases in study I (n = 40) and silver-impregnated cases in study II (n = 41) were used in conjunction with AQuify(Â®) and CLs (Balafilcon A). Cases were replaced monthly and collected at 1, 3 and 4 (for silver-impregnated cases only) months. Regular cases and the 4(th) month silver-impregnated cases were maintained 'dry' and other cases were maintained 'wet' between uses. At collection, storage cases were sampled and cultured for microbial identification and enumeration. Ocular clinical findings, subjective responses to CL wear and compliance were recorded at each visit.Results:The percentage of microbial contamination for silver-impregnated and regular cases was 71% and 82% respectively. There were significantly (p

Recurrent Urinary Tract Infection and Urinary Escherichia Coli in Women Ingesting Cranberry Juice Daily: a Randomized Controlled Trial Mayo Clinic Proceedings. Mayo Clinic. Feb, 2012 | Pubmed ID: 22305026 To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice daily.

Metabolic Syndrome: Definition and Therapeutic Implications Postgraduate Medicine. Jan, 2012 | Pubmed ID: 22314111 The collection of impaired glucose metabolism, central obesity, elevated blood pressure, and dyslipidemia is identified as metabolic syndrome (MetS). It is estimated that approximately 25% of the world's population has MetS. In the United States, MetS is more common in men and Hispanics, and its incidence increases with age. Metabolic syndrome increases the risk of developing cardiovascular disease and type 2 diabetes mellitus. The underlying risk factors include insulin resistance and abdominal obesity. Confusion about MetS exists in part due to the lack of a consensus definition and treatment protocol. Treatment of MetS begins with therapeutic lifestyle changes and then pharmacologic treatment of the syndrome's individual components. Effective interventions include diet modification, exercise, and use of pharmacologic agents to treat risk factors. Weight loss and increasing physical activity significantly improve all aspects of MetS. A diet that includes more fruits, vegetables, whole grains, monounsaturated fats, and low-fat dairy products will benefit most patients with MetS. Physicians can be most effective in advising patients by customizing specific lifestyle recommendations after assessing patients for the presence of risk factors.

Work-related Musculoskeletal Discomfort and Injuries in Australian Optometrists Work (Reading, Mass.). 2012 | Pubmed ID: 22316987 Work-related musculoskeletal discomfort and injuries are reported by optometrists. The purpose of this paper is to describe the process used to investigate work-related discomfort in Australian optometrists. A multistage project was conducted which included questionnaires, interviews and onsite observations. Participants, with and without self-reported discomfort, included clinical optometrists, optometry students and clinical teachers. The various stages of the study developed over the course of the project, primarily in response to results collected at various stages. A multistage approach proved valuable for confirming results and testing hypotheses, and for investigating different groups of workers (clinicians, teachers and students). General guidelines to reduce the risk of work-related discomfort in optometrists can be developed from this project. Specific recommendations and teaching curricula have been identified in this project as areas of future research and development.

Cefpodoxime Vs Ciprofloxacin for Short-course Treatment of Acute Uncomplicated Cystitis: a Randomized Trial JAMA : the Journal of the American Medical Association. Feb, 2012 | Pubmed ID: 22318279 Although fluoroquinolones remain the most reliable urinary antimicrobial, resistance rates have increased and effective fluoroquinolone-sparing antimicrobials are needed.

GB Virus C: the Good Boy Virus? Trends in Microbiology. Mar, 2012 | Pubmed ID: 22325031 GB virus C (GBV-C) is a lymphotropic human virus discovered in 1995 that is related to hepatitis C virus (HCV). GBV-C infection has not been convincingly associated with any disease; however, several studies found an association between persistent GBV-C infection and improved survival in HIV-positive individuals. GBV-C infection modestly alters T cell homeostasis in vivo through various mechanisms, including modulation of chemokine and cytokine release and receptor expression, and by diminution of T cell activation, proliferation and apoptosis, all of which may contribute to improved HIV clinical outcomes. In vitro studies confirm these clinical observations and demonstrate an anti-HIV replication effect of GBV-C. This review summarizes existing data on potential mechanisms by which GBV-C interferes with HIV, and the research needed to capitalize on this epidemiological observation.

A New Whole Genome Amplification Method for Studying Clonal Evolution Patterns in Malignant Colorectal Polyps Genes, Chromosomes & Cancer. May, 2012 | Pubmed ID: 22334367 To identify the genetic drivers of colorectal tumorigenesis, we applied array comparative genomic hybridization (aCGH) to 13 formalin-fixed paraffin-embedded (FFPE) samples of early, localized human colon adenocarcinomas arising in high-grade adenomas (so-called "malignant polyps"). These lesions are small and hence the amount of DNA is limited. Additionally, the quality of DNA is compromised due to the fragmentation as a consequence of formalin fixation. To overcome these problems, we optimized a newly developed isothermal whole genome amplification system (NuGEN OvationÂ® WGA FFPE System). Starting with 100 ng of FFPE DNA, the amplification system produced 4.01 Â± 0.29 Î¼g (mean Â± standard deviation) of DNA. The excellent quality of amplified DNA was further indicated by a high signal-to-noise ratio and a low derivative log(2) ratio spread. Both, the amount of amplified DNA and aCGH performance were independent of the age of the FFPE blocks and the associated degradation of the extracted DNA. We observed losses of chromosome arms 5q and 18q in the adenoma components of the malignant polyp samples, while the embedded early carcinomas revealed losses of 8p, 17p, and 18, and gains of 7, 13, and 20. Aberrations detected in the adenoma components were invariably maintained in the embedded carcinomas. This approach demonstrates that using isothermally whole genome amplified FFPE DNA is technically suitable for aCGH. In addition to demonstrating the clonal origin of the adenoma and carcinoma part within a malignant polyp, the gain of chromosome arm 20q was an indicator for progression from adenoma to carcinoma.

AMP-activated Protein Kinase Î²-subunit Requires Internal Motion for Optimal Carbohydrate Binding Biophysical Journal. Jan, 2012 | Pubmed ID: 22339867 AMP-activated protein kinase interacts with oligosaccharides and glycogen through the carbohydrate-binding module (CBM) containing the Î²-subunit, for which there are two isoforms (Î²(1) and Î²(2)). Muscle-specific Î²(2)-CBM, either as an isolated domain or in the intact enzyme, binds carbohydrates more tightly than the ubiquitous Î²(1)-CBM. Although residues that contact carbohydrate are strictly conserved, an additional threonine in a loop of Î²(2)-CBM is concurrent with an increase in flexibility in Î²(2)-CBM, which may account for the affinity differences between the two isoforms. In contrast to Î²(1)-CBM, unbound Î²(2)-CBM showed microsecond-to-millisecond motion at the base of a Î²-hairpin that contains residues that make critical contacts with carbohydrate. Upon binding to carbohydrate, similar microsecond-to-millisecond motion was observed in this Î²-hairpin and the loop that contains the threonine insertion. Deletion of the threonine from Î²(2)-CBM resulted in reduced carbohydrate affinity. Although motion was retained in the unbound state, a significant loss of motion was observed in the bound state of the Î²(2)-CBM mutant. Insertion of a threonine into the background of Î²(1)-CBM resulted in increased ligand affinity and flexibility in these loops when bound to carbohydrate. However, these mutations indicate that the additional threonine is not solely responsible for the differences in carbohydrate affinity and protein dynamics. Nevertheless, these results suggest that altered protein dynamics may contribute to differences in the ligand affinity of the two naturally occurring CBM isoforms.

Receptor Chimeras Demonstrate That the C-terminal Domain of the Human Cytomegalovirus US27 Gene Product is Necessary and Sufficient for Intracellular Receptor Localization Virology Journal. 2012 | Pubmed ID: 22339884 Human cytomegalovirus (HCMV) is ubiquitous in the population but generally causes only mild or asymptomatic infection except in immune suppressed individuals. HCMV employs numerous strategies for manipulating infected cells, including mimicry of G-protein coupled receptors (GPCRs). The HCMV US27 gene product is a putative GPCR, yet no ligand or signaling has been identified for this receptor. In the present study, immunofluorescence microscopy was used to examine the cellular distribution of wild type US27, as well as US27 deletion mutants and chimeric receptors.

Identification of Conserved Antigens from Staphylococcal and Streptococcal Pathogens Journal of Medical Microbiology. Jun, 2012 | Pubmed ID: 22345598 The design of vaccines containing epitopes shared between different human pathogens may lead to cross-species protection. In order to identify potentially conserved bacterial antigens, bacteriophage expression libraries of genomic DNA from Streptococcus agalactiae, Streptococcus pneumoniae and Streptococcus pyogenes were probed with human sera from Staphylococcus aureus-infected and healthy individuals. By comparison with previous screening data from Staphylococcus epidermidis and Staph. aureus, putative antigenic, conserved domains across the genera were identified. In particular, three potentially antigenic conserved regions were identified based on the N-terminal domain of SACOL0609 (SdrD), the C-terminal domain of SACOL0723 (ScaB) and the C-terminus of SACOL1140 (IsdA) from Staph. aureus. The three domains were overexpressed, recombinant proteins were purified and polyclonal antisera raised against them recognized cell surface-located proteins from both staphylococcal and streptococcal species. The antisera were also able to opsonize both Staph. aureus and Strep. agalactiae thereby increasing their phagocytic uptake by human neutrophils. The conserved antigenic domains therefore represent potential cross-protective vaccine candidates.

Efficient Synthesis and Biological Evaluation of Proximicins A, B and C Bioorganic & Medicinal Chemistry. Mar, 2012 | Pubmed ID: 22364744 A quick and efficient synthesis and the biological evaluation of promising antitumor-antibiotics proximicins A, B and C are reported. The characteristic repetitive unit of these molecules, the methyl 4-Boc-aminofuran-2-carboxylate 15, was prepared in three synthetic steps in good yield using an optimised copper-catalysed amidation method. The proximicins were evaluated for their antitumor activity using cellular methods. Proximicin B induced apoptosis in both Hodgkin's lymphoma and T-cell leukemia cell lines and proximicin C exhibited significantly high cytotoxicity against glioblastoma and breast carcinoma cells. The proximicins were also screened against Escherichia coli, Enterococcus faecalis and several strains of methicillin-and multidrug-resistant Staphylococcus aureus. Proximicin B showed noteworthy activity against antibiotic-resistant Gram-positive cocci.

Long-range Transcriptional Control of an Operon Necessary for Virulence-critical ESX-1 Secretion in Mycobacterium Tuberculosis Journal of Bacteriology. May, 2012 | Pubmed ID: 22389481 The ESX-1 secretion system of Mycobacterium tuberculosis has to be precisely regulated since the secreted proteins, although required for a successful virulent infection, are highly antigenic and their continued secretion would alert the immune system to the infection. The transcription of a five-gene operon containing espACD-Rv3613c-Rv3612c, which is required for ESX-1 secretion and is essential for virulence, was shown to be positively regulated by the EspR transcription factor. Thus, transcription from the start site, found to be located 67 bp upstream of espA, was dependent upon EspR enhancer-like sequences far upstream (between 884 and 1,004 bp), which we term the espA activating region (EAR). The EAR contains one of the known binding sites for EspR, providing the first in vivo evidence that transcriptional activation at the espA promoter occurs by EspR binding to the EAR and looping out DNA between this site and the promoter. Regulation of transcription of this operon thus takes place over long regions of the chromosome. This regulation may differ in some members of the M. tuberculosis complex, including Mycobacterium bovis, since deletions of the intergenic region have removed the upstream sequence containing the EAR, resulting in lowered espA expression. Consequent differences in expression of ESX-1 in these bacteria may contribute to their various pathologies and host ranges. The virulence-critical nature of this operon means that transcription factors controlling its expression are possible drug targets.

FT011, a New Anti-fibrotic Drug, Attenuates Fibrosis and Chronic Heart Failure in Experimental Diabetic Cardiomyopathy European Journal of Heart Failure. May, 2012 | Pubmed ID: 22417655 Cardiac remodelling in diabetes includes pathological accumulation of extracellular matrix and myocyte hypertrophy that contribute to heart dysfunction. Attenuation of remodelling represents a potential therapeutic target. We tested this hypothesis using a new anti-fibrotic drug, FT011 (Fibrotech Therapeutics Pty Ltd), on diabetic Ren-2 rats, a model which replicates many of the structural and functional manifestations of diabetic cardiomyopathy in humans.

Total Extrusion of the Cuboid: a Case Report Clinics in Podiatric Medicine and Surgery. Apr, 2012 | Pubmed ID: 22424493 The incidence of total extrusion of the cuboid is rare, without any known published data or surgical guidelines. This case report describes the management of an open extruded cuboid by staged surgical interventions. Arthrodesis of the lateral column with a structural bone graft is a viable option to address the shortening, instability, and severe bone loss caused by the total cuboid extrusion.

A Comparison of Predictive Equations of Energy Expenditure and Measured Energy Expenditure in Critically Ill Patients Journal of Critical Care. Jun, 2012 | Pubmed ID: 22425340 Multiple equations exist for predicting resting energy expenditure (REE). The accuracy of these for estimating energy requirements of critically ill patients is not clear, especially for obese patients. We sought to compare REE, calculated with published formulas, with measured REE in a cohort of mechanically ventilated subjects.

An Update in Incretin-based Therapy: a Focus on Dipeptidyl Peptidase--4 Inhibitors Current Diabetes Reviews. May, 2012 | Pubmed ID: 22429011 Dipeptidyl peptidase -4 inhibitors represent a novel way to augment the incretin system and one of the newest class of medications in the treatment of type 2 diabetes mellitus. Their mechanism of action is to decrease the inactivation of glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide, both of which are involved in maintaining euglycemia subsequent to carbohydrate intake. Currently investigated agents include sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin. Each agent has been shown to provide significant improvements in glycemic control compared to placebo. They are effective when added to other oral diabetes agents and in the cases of sitagliptin, vildagliptin, and alogliptin in addition to insulin. These agents may not provide as significant improvement in glucose concentrations as some other medications including metformin, thiazolidinediones, or glucagon-like peptide 1 agonists. The lack of head to head clinical data comparing the various dipeptidyl peptidase 4 inhibitors does not allow for specific recommendations if one agent is more effective or safer than another within the class. Their side effect profile suggests they are very well tolerated and have few drug interactions. For patients with mildly elevated glucose concentrations, they are therapeutic options in both drug-naive patients as well as those not optimally controlled on other diabetes medications.

Congenital Cholesteatoma: Predictors for Residual Disease and Hearing Outcomes Archives of Otolaryngology--head & Neck Surgery. Mar, 2012 | Pubmed ID: 22431873 To determine predictive factors for residual disease and hearing outcomes of surgery for congenital cholesteatoma (CC).

Transmission of GB Virus Type C Via Transfusion in a Cohort of HIV-infected Patients The Journal of Infectious Diseases. May, 2012 | Pubmed ID: 22438325 GB virus C (GBV-C) infection is transmitted by blood exposure and associated with lower human immunodeficiency virus (HIV) load and slower HIV disease progression. Few studies describe predictors of acute GBV-C infection following transfusion in HIV-infected patients.

Mycobacterium Tuberculosis WhiB1 Represses Transcription of the Essential Chaperonin GroEL2 Tuberculosis (Edinburgh, Scotland). Jul, 2012 | Pubmed ID: 22464736 A central feature of TB pathogenesis is the formation of Mycobacterium tuberculosis latent infections that can persist for decades. Nitric oxide produced by infected lung macrophages promotes expression of genes associated with dormancy, and impaired nitric oxide production can lead to reactivation of latent disease. Recently, WhiB1 was identified as a nitric oxide-responsive transcription factor. Here it is shown that apo-WhiB1 binds to groEL2 (Rv0440) promoter DNA. Apo-WhiB1 inhibited transcription from the groEL2 promoter in vitro and the transcript start was located âˆ¼181 bases upstream of the groEL2 start codon. Electrophoretic mobility shift assays with sub-fragments of the groEL2 promoter indicated that the complete Rv0439c-Rv0440 intergenic region was required for WhiB1 binding, suggesting that this region possessed more than one WhiB1-binding site. DNase I footprinting identified a WhiB1-binding region that overlapped the -35 element of the groEL2 promoter. The CRP-family transcription factor Cmr (Rv1675c) was shown to bind the groEL2 promoter and activate transcription in vitro in the presence or absence of cAMP. Therefore, it is suggested that WhiB1 acts to oppose Cmr-mediated cAMP-independent activation of groEL2 expression in the presence of nitric oxide by promoter occlusion.

Cortisol and Interleukin-6 Responses During Intermittent Exercise in Two Different Hot Environments with Equivalent WBGT Journal of Occupational and Environmental Hygiene. 2012 | Pubmed ID: 22482790 Blood marker concentrations such as cortisol (COR) and interleukin (IL)-6 are commonly used to evaluate the physiological strain associated with work in the heat. It is unclear, however, if hot environments of an equivalent thermal stress, as defined by a similar wet bulb globe temperature (WBGT), result in similar response patterns. This study examined markers of neuroendocrine (COR) and immune (IL-6) responses, as well as the cardiovascular and thermal responses, relative to changes in body heat content measured by whole-body direct calorimetry during work in two different hot environments with equivalent WBGT. Eight males performed a 2-hr heavy intermittent exercise protocol (six 15-min bouts of cycling at a constant rate of metabolic heat production (360W) interspersed by 5-min rest periods) in Hot/Dry (46Â°C, 10% relative humidity [RH]) and Warm/Humid (33Â°C, 60% RH) conditions (WBGT âˆ¼ 29Â°C). Whole-body evaporative and dry heat exchange, change in body heat content (Î”H(b)), rectal temperature (T(re)), and heart rate were measured continuously. Venous blood was obtained at rest (PRE) and the end of each exercise bout for the measurement of changes in plasma volume (PV), plasma protein (an estimate of plasma water changes), COR, and IL-6. Ratings of perceived exertion and thermal sensation were measured during the last minute of each exercise bout. No differences existed for Î”H(b), heart rate, T(re),%Î”PV, plasma protein concentration, perceptual strain (thermal sensation, perceived exertion), and COR between the Hot/Dry and Warm/Humid conditions. IL-6 exhibited an interaction effect (p = 0.041), such that greater increases were observed in the Hot/Dry (Î” = 1.61 pgÂ·mL(-1)) compared with the Warm/Humid (Î” = 0.64 pgÂ·mL(-1)) environment. These findings indicate that work performed in two different hot environments with equivalent WBGT resulted in similar levels of thermal, cardiovascular, and perceptual strain, which support the use of the WBGT stress index. However, the greater IL-6 response in the Hot/Dry requires further research to elucidate the effects of different hot environments and work intensities.

Association of Single Nucleotide Polymorphisms of Interleukins-1Î², -6, and -12B with Contact Lens Keratitis Susceptibility and Severity Ophthalmology. Jul, 2012 | Pubmed ID: 22503230 To investigate whether single nucleotide polymorphisms (SNPs) in interleukin (IL)-1Î², IL-6, and IL-12Î² are associated with the susceptibility and severity of contact lens-related keratitis.

Risk Factors for Moderate and Severe Microbial Keratitis in Daily Wear Contact Lens Users Ophthalmology. Aug, 2012 | Pubmed ID: 22521083 To establish risk factors for moderate and severe microbial keratitis among daily contact lens (CL) wearers in Australia.

How Do Australian Optometrists Manage Work-related Physical Discomfort? Clinical & Experimental Optometry : Journal of the Australian Optometrical Association. Nov, 2012 | Pubmed ID: 22530621 Work-related physical discomfort exists within the optometric profession. It is not well understood how optometrists manage this issue in their workplaces.

GB Virus Type C Infection Polarizes T-cell Cytokine Gene Expression Toward a Th1 Cytokine Profile Via NS5A Protein Expression The Journal of Infectious Diseases. Jul, 2012 | Pubmed ID: 22535999 Human immunodeficiency virus (HIV) disease progression is associated with a helper T cell 1 (Th1) to helper T cell 2 (Th2) cytokine profile switch. Persistent GB virus type C (GBV-C) infection is associated with survival and a serum Th1 cytokine profile in HIV-infected individuals. We found that GBV-C infection increased gene expression of Th1 cytokines and decreased Th2 cytokine expression in peripheral blood mononuclear cells. Furthermore, expression of GBV-C NS5A protein in a CD4(+) cell line resulted in upregulation of Th1 cytokines (tumor necrosis factor Î±) and downregulation of Th2 cytokines (interleukin 4, interleukin 5, interleukin 10, interleukin 13). GBV-C-induced modulation in T-cell cytokines may contribute to the beneficial effect of GBV-C in HIV-infected individuals.

Characteristics and Comparative Performance of Direct Culture, Direct PCR and Enumeration Methods for Detection and Quantification of Campylobacter Spp. in Broiler Caeca Veterinary Microbiology. Oct, 2012 | Pubmed ID: 22565009 Detection and enumeration of Campylobacter spp. in broiler chicken flocks are key components of research and surveillance studies aimed at reducing Campylobacter infections in people. Direct culture of caecal contents onto selective agar is the typical method used to confirm flock colonisation. Modified charcoal cefoperazone deoxycholate agar (mCCDA) is commonly used for this method, although alternative selective media have been used. Additionally, PCR methods to detect Campylobacter DNA from caecal contents may provide a rapid alternative. However comparative performance data for these methods is limited and therefore required to ensure optimal detection methods for this sample type. In this study, 306 broiler caeca were tested for Campylobacter using direct culture on mCCDA, Skirrows and Preston agars and two real-time PCR methods, one specific for mapA/ceuE regions and another for the flaA gene region. Additionally, the suitability of spread plating and spiral plating methods for enumeration of Campylobacter and the impact of sample storage were assessed. This study confirmed modified CCDA as an optimal media for detection of Campylobacter in broiler caeca. It was significantly more sensitive than Skirrows or Preston agars. This study also demonstrated that the mapA/ceuE PCR had excellent agreement with culture on mCCDA and is a genuine alternative method. Spread plating and spiral plating methods were suitable for enumeration although spiral plating appeared more sensitive for stored samples (72 h). A 1 log reduction in viable Campylobacters was observed in stored samples, therefore storage effects should be considered for quantitative studies with broiler caeca.

In Vitro Metabolism of the Brominated Flame Retardants 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB) and Bis(2-ethylhexyl) 2,3,4,5-tetrabromophthalate (TBPH) in Human and Rat Tissues Chemical Research in Toxicology. Jul, 2012 | Pubmed ID: 22575079 Due to the phaseout of polybrominated diphenyl ether (PBDE) flame retardants, new chemicals, such as 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB) and bis(2-ethylhexyl) 2,3,4,5-tetrabromophthalate (TBPH), have been used as replacements in some commercial flame retardant mixtures. Both chemicals have been detected in indoor dust at concentrations approaching the concentrations of PBDEs; however, little is known about their fate, metabolism, or toxicity. The goal of this study was to investigate the potential metabolism of these two brominated flame retardants in human and rat tissues by conducting in vitro experiments with liver and intestinal subcellular fractions. In all the experiments, TBB was consistently metabolized to 2,3,4,5-tetrabromobenzoic acid (TBBA) via cleavage of the 2-ethylhexyl chain without requiring any added cofactors. TBBA was also formed in purified porcine carboxylesterase but at a much faster rate of 6.29 Â± 0.58 nmol min(-1) mg protein(-1). The estimated K(m) and V(max) values for TBB metabolism in human microsomes were 11.1 Â± 3.9 Î¼M and 0.644 Â± 0.144 nmol min(-1) mg protein(-1), respectively. A similar K(m) of 9.3 Â± 2.2 Î¼M was calculated for porcine carboxylesterase, indicating similar enzyme specificity. While the rapid formation of TBBA may reduce the bioaccumulation potential of TBB in mammals and may be useful as a biomarker of TBB exposure, the toxicity of this brominated benzoic acid is unknown and may be a concern based on its structural similarity to other toxic pollutants. In contrast to TBB, no metabolites of TBPH were detected in human or rat subcellular fractions. However, a metabolic product of TBPH, mono(2-ethylhexyl) tetrabromophthalate (TBMEHP), was formed in purified porcine carboxylesterase at an approximate rate of 1.08 pmol min(-1) mg protein(-1). No phase II metabolites of TBBA or TBMEHP were observed. More research is needed to understand the in vivo toxicokinetics and health effects of these compounds given their current ubiquitous presence in most US households and the resulting probability of chronic exposure, particularly to young children.

Structural Characterization and Antimicrobial Evaluation of Atractyloside, Atractyligenin, and 15-didehydroatractyligenin Methyl Ester Journal of Natural Products. Jun, 2012 | Pubmed ID: 22594797 We report the first complete structure elucidation of the ent-kaurane diterpenoid glycoside atractyloside (1) by means of NMR and X-ray diffractometry techniques. Extensive one- and two-dimensional NMR experiments were employed to assign the proton and carbon signals of 1, and crystallography experiments established the configurations of all stereogenic centers. Furthermore, we present a novel semisynthetic route for the preparation of the highly cytotoxic aglycone derivative of 1, 15-didehydroatractyligenin methyl ester (3). All compounds were tested for their antibiotic activity against Enterococcus faecalis, Escherichia coli, and several strains of Staphylococcus aureus, including fluoroquinolone-resistant (SA1199B) and two epidemic MRSA (EMRSA-15 and -16) strains. Compound 3 exhibited moderate activity against all of the Staph. aureus strains with an MIC value of 128 mg/L.

Characterization of a Peptide Domain Within the GB Virus C Envelope Glycoprotein (E2) That Inhibits HIV Replication Virology. Aug, 2012 | Pubmed ID: 22608061 GB virus C (GBV-C) infection is associated with prolonged survival in HIV-infected cohorts, and GBV-C E2 protein inhibits HIV entry when added to CD4+ T cells. To further characterize E2 effects on HIV replication, stably transfected Jurkat cell lines expressing GBV-C E2 or control sequences were infected with HIV and replication was measured. HIV replication (all 6 isolates studied) was inhibited in all cell lines expressing a region of 17 amino acids of GBV-C E2, but not in cell lines expressing E2 without this region. In contrast, mumps and yellow fever virus replication was not inhibited by E2 protein expression. Synthetic GBV-C E2 17mer peptides did not inhibit HIV replication unless they were fused to a tat-protein-transduction-domain (TAT) for cellular uptake. These data identify the region of GBV-C E2 protein involved in HIV inhibition, and suggest that this GBV-C E2 peptide must gain entry into the cell to inhibit HIV.

Feeling the Strain: Predicting the Third Dimension of Core Affect The Behavioral and Brain Sciences. Jun, 2012 | Pubmed ID: 22617674 This commentary (1) raises the question about the possible conflation of core affect with the neural representation of interoceptive changes in regard to whether biological value is subpersonal or must be experienced, and (2) proposes that Wundt's third dimension of core affect - strain-relaxation - can be accounted for in the target model under a generalised predictive model of attention.

Tsc2, a Positional Candidate Gene Underlying a Quantitative Trait Locus for Hepatic Steatosis Journal of Lipid Research. Aug, 2012 | Pubmed ID: 22628617 Nonalchoholic fatty liver disease (NAFLD) is the most common cause of liver dysfunction and is associated with metabolic diseases, including obesity, insulin resistance, and type 2 diabetes. We mapped a quantitative trait locus (QTL) for NAFLD to chromosome 17 in a cross between C57BL/6 (B6) and BTBR mouse strains made genetically obese with the Lep(ob/ob) mutation. We identified Tsc2 as a gene underlying the chromosome 17 NAFLD QTL. Tsc2 functions as an inhibitor of mammalian target of rapamycin, which is involved in many physiological processes, including cell growth, proliferation, and metabolism. We found that Tsc2(+/-) mice have increased lipogenic gene expression in the liver in an insulin-dependent manner. The coding single nucleotide polymorphism between the B6 and BTBR strains leads to a change in the ability to inhibit the expression of lipogenic genes and de novo lipogenesis in AML12 cells and to promote the proliferation of Ins1 cells. This difference is due to a different affinity of binding to Tsc1, which affects the stability of Tsc2.

In Vitro Magnetic Resonance Imaging Evaluation of Ossicular Implants at 3 T Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. Jul, 2012 | Pubmed ID: 22643444 Ossicular implants made from metallic materials may be acceptable or pose hazards for patients referred for magnetic resonance imaging (MRI) examinations, depending on the outcome of proper MRI testing procedures.

Perceived Partner Support in Pregnancy Predicts Lower Maternal and Infant Distress Journal of Family Psychology : JFP : Journal of the Division of Family Psychology of the American Psychological Association (Division 43). Jun, 2012 | Pubmed ID: 22662772 Maternal postpartum emotional distress is quite common and can pose significant risk to mothers and infants. The current study investigated mothers' relationships with their partners during pregnancy and tested the hypotheses that perception of prenatal partner support is a significant predictor of changes in maternal emotional distress from midpregnancy to postpartum, and contributes to maternal ratings of infant distress to novelty. Using a prospective longitudinal design, 272 adult pregnant women were interviewed regarding their partner support, relationship satisfaction, and interpersonal security (attachment style and willingness to seek out support), and they completed standardized measures of prenatal symptoms of depression and anxiety (distress). At 6 to 8 weeks' postpartum, mothers reported these symptoms again and completed measures of their infants' temperament. Structural equation modeling (SEM) was used to test direct and indirect contributions of partner support, relationship satisfaction, and interpersonal security to maternal and infant postpartum distress. Mothers who perceived stronger social support from their partners midpregnancy had lower emotional distress postpartum after controlling for their distress in early pregnancy, and their infants were reported to be less distressed in response to novelty. Partner support mediated the effects of mothers' interpersonal security and relationship satisfaction on maternal and infant outcomes. A high-quality, supportive partner relationship during pregnancy may contribute to improved maternal and infant well-being postpartum, indicating a potential role for partner relationships in mental health interventions, with possible benefits for infants as well.

Premorbid Multivariate Markers of Neurodevelopmental Instability in the Prediction of Adult Schizophrenia-spectrum Disorder: a High-risk Prospective Investigation Schizophrenia Research. Aug, 2012 | Pubmed ID: 22664169 The authors examined whether multiple childhood indicators of neurodevelopmental instability known to relate to schizophrenia-spectrum disorders could predict later schizophrenia-spectrum outcomes. A standardized battery of neurological and intellectual assessments was administered to a sample of 265 Danish children in 1972, when participants were 10-13 years old. Parent psychiatric diagnoses were also obtained in order to evaluate the predictive strength of neurodevelopmental factors in combination with genetic risk. Adult diagnostic information was available for 244 members of the sample. Participants were grouped into three categories indicating level of genetic risk: children with a parent with schizophrenia (n=94); children with a parent with a non-psychotic mental health diagnosis (n=84); and children with a parent with no records of psychiatric hospitalization (n=66). Variables measured included minor physical anomalies (MPAs), coordination, ocular alignment, laterality, and IQ. Adult diagnoses were assessed through psychiatric interviews in 1992, as well as through a scan of the national psychiatric registry through 2007. Through a combination of multiple childhood predictors, the model correctly classified 73% (24 of 33) of the participants who eventually developed a schizophrenia-spectrum outcome in adulthood. Results suggest that, with replication, multivariate premorbid prediction could potentially be a useful complementary approach to identifying individuals at risk for developing a schizophrenia-spectrum disorder. Genetic risk, MPAs, and other markers of neurodevelopmental instability may be useful for comprehensive prediction models.

Study Design May Explain Discrepancies in GB Virus C Effects on Interferon-Î³ and Interleukin-2 Production and CD38 Expression in T Lymphocytes MemÃ³rias Do Instituto Oswaldo Cruz. Jun, 2012 | Pubmed ID: 22666874

Effect of Chromium Dinicocysteinate Supplementation on Circulating Levels of Insulin, TNF-Î±, Oxidative Stress, and Insulin Resistance in Type 2 Diabetic Subjects: Randomized, Double-blind, Placebo-controlled Study Molecular Nutrition & Food Research. Aug, 2012 | Pubmed ID: 22674882 Chromium and cysteine supplementation have been shown to improve glucose metabolism in animal studies. This study examined the hypothesis that chromium dinicocysteinate (CDNC), a complex of chromium and l-cysteine, is beneficial in lowering oxidative stress, vascular inflammation, and glycemia in type 2 diabetic subjects.

Body Heat Storage During Intermittent Work in Hot-dry and Warm-wet Environments Applied Physiology, Nutrition, and Metabolism = Physiologie AppliquÃ©e, Nutrition Et MÃ©tabolisme. Oct, 2012 | Pubmed ID: 22686402 We examined heat balance using an American Conference of Governmental Industrial Hygienists threshold limit value allocated exercise protocol in hot-dry (HD; 46 Â°C, 10% relative humidity (RH)) and warm-wet (WW; 33 Â°C, 60% RH) environments of equivalent WBGT (29 Â°C) for different clothing ensembles. Whole-body heat exchange and changes in body heat content (Î”H(b)) were measured using simultaneous direct whole-body and indirect calorimetry. Eight males performed six 15-min cycling periods at a constant rate of metabolic heat production (360 W) interspersed by 5-min rest periods for six experimental trials: HD and WW environments for a seminude control (CON), modified work uniform (MWU, moisture permeable top and work pants), and standard work uniform (SWU, work coveralls and cotton undergarments). Whole-body evaporative and dry heat exchange, rectal temperature (T(re)), and heart rate were measured continuously. The cumulative Î”H(b) during the 2 h intermittent exercise protocol was similar between HD and WW environments for each of the clothing ensembles (CON, 387 Â± 55 vs. 435 Â± 49 kJ; MWU, 485 Â± 58 vs. 531 Â± 61 kJ; SWU, 585 Â± 74 vs. 660 Â± 54 kJ, respectively). Similarly, no differences in T(re) (CON, 37.67 Â± 0.07 vs. 37.48 Â± 0.08 Â°C; MWU, 37.73 Â± 0.08 vs. 37.53 Â± 0.09 Â°C; SWU, 38.01 Â± 0.09 vs. 37.94 Â± 0.05 Â°C) or heat rate (CON, 93 Â± 3 vs. 84 Â± 3 beatsÂ·minâ»Â¹; MWU, 102 Â± 5 vs. 95 Â± 9 beatsÂ·minâ»Â¹; SWU, 119 Â± 8 vs. 110 Â± 9 beatsÂ·minâ»Â¹) were observed at the end of the 2 h intermittent exercise protocol in HD vs. WW environments, respectively. We showed similar levels of thermal and cardiovascular strain for intermittent work performed in high heat stress conditions of varying environmental conditions but similar WBGT.

Acute ST-segment Elevation Myocardial Infarction: A Rare Initial Presentation of Previously Undiagnosed Essential Thrombocythemia Platelets. 2012 | Pubmed ID: 22686448 Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by hemorrhagic and thrombotic complications. We describe a rare case of ST-segment elevation myocardial infarction (STEMI) in a patient with previously undiagnosed ET, confirmed by gene mutation. A 68-year-old man presented with severe acute chest pain and was diagnosed with STEMI. Primary coronary angiography showed severe stenosis with thrombus in the proximal left anterior descending coronary artery. Percutaneous aspiration thrombectomy was performed with no residual stenosis. The patient was discharged on antiplatelet agents, aspirin, and clopidogrel. Further investigations for intracoronary thrombus with no underlying atherosclerotic disease revealed positive Janus kinase 2 (JAK2) V617F gene mutation, and this was consistent with a diagnosis of ET with elevated platelet count. This case describes a rare initial presentation of previously undiagnosed ET with acute STEMI and highlights the potential importance of secondary workup for non-atherosclerotic causes of STEMI with isolated intracoronary thrombus otherwise normal coronary vasculature with no focal atherosclerosis.

Long Range Transcriptional Control of Virulence Critical Genes in Mycobacterium Tuberculosis by Nucleoid-associated Proteins? Virulence. Jul, 2012 | Pubmed ID: 22722242

Surgical Reconstruction of the Diabetic Charcot Foot: Internal, External or Combined Fixation? Clinics in Podiatric Medicine and Surgery. Jul, 2012 | Pubmed ID: 22727382 Charcot neuroarthropathy of the foot and ankle is a devastating neuropathic complication that can eventually lead to a lower extremity amputation in the presence of an ulceration or infection. Current surgical approaches for the management of the diabetic Charcot foot and ankle deformities are largely based on expert opinions in various fixation methods attempting to avoid major postoperative complications. The goal of this article is to discuss the advantages and disadvantages of various internal, external, or combined fixation methods as they relate to the inherent challenges in the management of the diabetic Charcot foot.

GATA6 is Required for Proliferation, Migration, Secretory Cell Maturation, and Gene Expression in the Mature Mouse Colon Molecular and Cellular Biology. Sep, 2012 | Pubmed ID: 22733991 Controlled renewal of the epithelium with precise cell distribution and gene expression patterns is essential for colonic function. GATA6 is expressed in the colonic epithelium, but its function in the colon is currently unknown. To define GATA6 function in the colon, we conditionally deleted Gata6 throughout the epithelium of small and large intestines of adult mice. In the colon, Gata6 deletion resulted in shorter, wider crypts, a decrease in proliferation, and a delayed crypt-to-surface epithelial migration rate. Staining techniques and electron microscopy indicated deficient maturation of goblet cells, and coimmunofluorescence demonstrated alterations in specific hormones produced by the endocrine L cells and serotonin-producing cells. Specific colonocyte genes were significantly downregulated. In LS174T, the colonic adenocarcinoma cell line, Gata6 knockdown resulted in a significant downregulation of a similar subset of goblet cell and colonocyte genes, and GATA6 was found to occupy active loci in enhancers and promoters of some of these genes, suggesting that they are direct targets of GATA6. These data demonstrate that GATA6 is necessary for proliferation, migration, lineage maturation, and gene expression in the mature colonic epithelium.

The Effect of Sleep Apnea and Insomnia on Blood Levels of Leptin, Insulin Resistance, IP-10, and Hydrogen Sulfide in Type 2 Diabetic Patients Metabolic Syndrome and Related Disorders. Oct, 2012 | Pubmed ID: 22746298 Sleep deficits associated with sleep apnea and insomnia increase the risk of vascular inflammation and insulin resistance. This study examined the hypothesis that inflammation markers are higher in those diabetic patients who experience sleep deficits compared with those without any history of a sleep disorder.

Acquisition of GB Virus Type C and Lower Mortality in Patients with Advanced HIV Disease Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. Oct, 2012 | Pubmed ID: 22752515 GB virus type C (GBV-C) is transmitted by sexual or parenteral exposure and is prevalent among patients receiving blood products. GBV-C is associated with lower human immunodeficiency virus (HIV) RNA and better survival among HIV-infected patients. Open questions are the presence and the direction of any causal relationship between GBV-C infection and HIV disease markers in the context of highly active antiretroviral therapy (HAART).

Serum PBDEs in a North Carolina Toddler Cohort: Associations with Handwipes, House Dust, and Socioeconomic Variables Environmental Health Perspectives. Jul, 2012 | Pubmed ID: 22763040 Polybrominated diphenyl ethers (PBDEs) are persistent, bioaccumulative, and endocrine-disrupting chemicals.

Brominated and Chlorinated Flame Retardants in San Francisco Bay Sediments and Wildlife Environment International. Oct, 2012 | Pubmed ID: 22766500 Restrictions on the use of polybrominated diphenyl ethers (PBDEs) have resulted in the use of alternative flame retardants in consumer products to comply with flammability standards. In contrast to PBDEs, information on the occurrence and fate of these alternative compounds in the environment is limited, particularly in the United States. In this study, a survey of flame retardants in San Francisco Bay was conducted to evaluate whether PBDE replacement chemicals and other current use flame retardants were accumulating in the Bay food web. In addition to PBDEs, brominated and chlorinated flame retardants (hexabromocyclododecane (HBCD) and Dechlorane Plus (DP)) were detected in Bay sediments and wildlife. Median concentrations of PBDEs, HBCD, and DP, respectively, were 4.3, 0.3, and 0.2 ng gâ»Â¹ dry weight (dw) in sediments; 1670,

The Siderophore Yersiniabactin Binds Copper to Protect Pathogens During Infection Nature Chemical Biology. Aug, 2012 | Pubmed ID: 22772152 Bacterial pathogens secrete chemically diverse iron chelators called siderophores, which may exert additional distinctive functions in vivo. Among these, uropathogenic Escherichia coli often coexpress the virulence-associated siderophore yersiniabactin (Ybt) with catecholate siderophores. Here we used a new MS screening approach to reveal that Ybt is also a physiologically favorable Cu(II) ligand. Direct MS detection of the resulting Cu(II)-Ybt complex in mice and humans with E. coli urinary tract infections demonstrates copper binding to be a physiologically relevant in vivo interaction during infection. Ybt expression corresponded to higher copper resistance among human urinary tract isolates, suggesting a protective role for this interaction. Chemical and genetic characterization showed that Ybt helps bacteria resist copper toxicity by sequestering host-derived Cu(II) and preventing its catechol-mediated reduction to Cu(I). Together, these studies reveal a new virulence-associated function for Ybt that is distinct from iron binding.

The Structure of Cardiac Glycogen in Healthy Mice International Journal of Biological Macromolecules. Dec, 2012 | Pubmed ID: 22782068 Transmission electron micrographs of glycogen extracted from healthy mouse hearts reveal aggregate structures around 133 nm in diameter. These structures are similar to, but on average somewhat smaller than, the Î±-particles of glycogen found in mammalian liver. Like the larger liver glycogens, these new particles in cardiac tissue appear to be aggregates of Î²-particles. Free Î²-particles are also present in liver, and are the only type of particle seen in skeletal muscle. They have diameters from 20 to 50 nm. We discuss the number distributions of glycogen particle diameters and the implications for the structure-function relationship of glycogens in these tissues. We point out the possible implications for the study of glycogen storage diseases, and of non-insulin dependent diabetes mellitus.

Immunogenicity and Safety of Varying Dosages of a Monovalent 2009 H1N1 Influenza Vaccine Given with and Without AS03 Adjuvant System in Healthy Adults and Older Persons The Journal of Infectious Diseases. Sep, 2012 | Pubmed ID: 22782949 Adjuvanted vaccines have the potential to improve influenza pandemic response. AS03 adjuvant has been shown to enhance the immune response to inactivated influenza vaccines. Methods: This trial was designed to evaluate the immunogenicity and safety of an inactivated 2009 H1N1 influenza vaccine at varying dosages of hemagglutinin with and without extemporaneously mixed AS03 adjuvant system in adults â‰¥ 18 years of age. Adults were randomized to receive 2 doses of 1 of 5 vaccine formulations (3.75 Âµg, 7.5 Âµg, or 15 Âµg with AS03 or 7.5 Âµg or 15 Âµg without adjuvant). Results: The study population included 544 persons

Structure-function Relationships of the Mycobacterium Tuberculosis Transcription Factor WhiB1 PloS One. 2012 | Pubmed ID: 22792304 Members of the WhiB-like (Wbl) protein family possess iron-sulfur clusters and are implicated in the regulation of developmental processes in Actinomycetes. Mycobacterium tuberculosis possesses seven Wbl proteins. The [4Fe-4S] cluster of M. tuberculosis WhiB1 is relatively insensitive to O(2) but very sensitive to nitric oxide (NO). Nitric oxide nitrosylates the WhiB1 iron-sulfur cluster and promotes DNA-binding; the apo-forms of WhiB1 also bind DNA. However, the molecular requirements for iron-sulfur cluster acquisition and for DNA-binding by WhiB1 are poorly characterized.

A Pilot Study of StopAdvisor: a Theory-based Interactive Internet-based Smoking Cessation Intervention Aimed Across the Social Spectrum Addictive Behaviors. Dec, 2012 | Pubmed ID: 22795643 This article reports a pilot study of a new smoking cessation website ('StopAdvisor'), which has been developed on the basis of PRIME theory, evidence, web-design expertise and user-testing. The aims were to i) evaluate whether cessation, website usage and satisfaction were sufficiently high to warrant a randomised controlled trial (RCT) and ii) assess whether outcomes were affected by socio-economic status.

Evaluating a Measure of Tanning Abuse and Dependence Archives of Dermatology. Jul, 2012 | Pubmed ID: 22801615 To evaluate the Structured Interview for Tanning Abuse and Dependence (SITAD).

Skin Cancer Screening Among Hispanic Adults in the United States: Results from the 2010 National Health Interview Survey Archives of Dermatology. Jul, 2012 | Pubmed ID: 22801634

Factors Affecting Hatch Success of Hawksbill Sea Turtles on Long Island, Antigua, West Indies PloS One. 2012 | Pubmed ID: 22802928 Current understanding of the factors influencing hawksbill sea turtle (Eretmochelys imbricata) hatch success is disparate and based on relatively short-term studies or limited sample sizes. Because global populations of hawksbills are heavily depleted, evaluating the parameters that impact hatch success is important to their conservation and recovery. Here, we use data collected by the Jumby Bay Hawksbill Project (JBHP) to investigate hatch success. The JBHP implements saturation tagging protocols to study a hawksbill rookery in Antigua, West Indies. Habitat data, which reflect the varied nesting beaches, are collected at egg deposition, and nest contents are exhumed and categorized post-emergence. We analyzed hatch success using mixed-model analyses with explanatory and predictive datasets. We incorporated a random effect for turtle identity and evaluated environmental, temporal and individual-based reproductive variables. Hatch success averaged 78.6% (SD: 21.2%) during the study period. Highly supported models included multiple covariates, including distance to vegetation, deposition date, individual intra-seasonal nest number, clutch size, organic content, and sand grain size. Nests located in open sand were predicted to produce 10.4 more viable hatchlings per clutch than nests located >1.5 m into vegetation. For an individual first nesting in early July, the fourth nest of the season yielded 13.2 more viable hatchlings than the initial clutch. Generalized beach section and inter-annual variation were also supported in our explanatory dataset, suggesting that gaps remain in our understanding of hatch success. Our findings illustrate that evaluating hatch success is a complex process, involving multiple environmental and individual variables. Although distance to vegetation and hatch success were inversely related, vegetation is an important component of hawksbill nesting habitat, and a more complete assessment of the impacts of specific vegetation types on hatch success and hatchling sex ratios is needed. Future research should explore the roles of sand structure, nest moisture, and local weather conditions.

Immune Defense Single Nucleotide Polymorphisms and Recruitment Strategies Associated with Contact Lens Keratitis Ophthalmology. Oct, 2012 | Pubmed ID: 22809755 To determine the association of single nucleotide polymorphisms (SNPs) of defensin 1B and toll-like receptor 4 with contact lens keratitis susceptibility and severity, and to understand the factors that influence study participation.

GB Virus C Envelope Protein E2 Inhibits TCR-induced IL-2 Production and Alters IL-2-signaling Pathways Journal of Immunology (Baltimore, Md. : 1950). Sep, 2012 | Pubmed ID: 22844114 GB virus type C (GBV-C) viremia is associated with reduced CD4+ T cell expansion following IL-2 therapy and with a reduction in T cell activation in HIV-infected individuals. The mechanism(s) by which GBV-C might alter T cell activation or IL-2 signaling have not been studied. In this study, we assess IL-2 release, IL-2R expression, IL-2 signaling, and cell proliferation in tet-off Jurkat cells expressing the GBV-C envelope glycoprotein (E2) following activation through the TCR. TCR activation was induced by incubation in anti-CD3/CD28 Abs. IL-2 release was measured by ELISA, STAT5 phosphorylation was assessed by immunoblot, and IL-2RÎ± (CD25) expression and cell proliferation were determined by flow cytometry. IL-2 and IL-2RÎ± steady-state mRNA levels were measured by real-time PCR. GBV-C E2 expression significantly inhibited IL-2 release, CD25 expression, STAT5 phosphorylation, and cellular proliferation in Jurkat cells following activation through the TCR compared with control cell lines. Reducing E2 expression by doxycycline reversed the inhibitory effects observed in the E2-expressing cells. The N-terminal 219 aa of E2 was sufficient to inhibit IL-2 signaling. Addition of purified recombinant GBV-C E2 protein to primary human CD4+ and CD8+ T cells inhibited TCR activation-induced IL-2 release and upregulation of IL-2RÎ± expression. These data provide evidence that the GBV-C E2 protein may contribute to the block in CD4+ T cell expansion following IL-2 therapy in HIV-infected individuals. Furthermore, the effects of GBV-C on IL-2 and IL-2-signaling pathways may contribute to the reduction in chronic immune activation observed in GBV-C/HIV-coinfected individuals.

An Update in Incretin-based Therapy: a Focus on Glucagon-like Peptide-1 Receptor Agonists Diabetes Technology & Therapeutics. Oct, 2012 | Pubmed ID: 22845681 The glucagon-like peptide-1 receptor agonists, exenatide and liraglutide, offer a unique mechanism in the treatment of type 2 diabetes mellitus (T2DM) as part of the incretin system. Their mechanism of action is to increase insulin secretion, decrease glucagon release, reduce food intake, and slow gastric emptying. They target postprandial blood glucose values and have some effect on fasting levels as well. In addition, they promote weight loss and may help to preserve Î²-cell function, both major problems in T2DM patients. Changes in hemoglobin A1c are similar to those produced by other T2DM agents, including thiazolidinediones, low-dose metformin, and sulfonylureas, and better than those caused by Î±-reductase inhibitors and dipeptidyl peptidase-4 inhibitors. These agents have been safely studied in combination with metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin therapy. Overall, data are limited for head-to-head comparisons, but it appears that liraglutide may have better efficacy and tolerability compared with exenatide; however, more studies are needed. They are overall well tolerated, with the main adverse events being similar to those with metformin (gastrointestinal intolerances that are transient and dose dependent). However, patients must be monitored for pancreatitis as a rare but possible side effect. For T2DM patients willing to use an injectable agent, exenatide and liraglutide offer another therapeutic option to control hyperglycemia with the potential for weight loss and may be combined with other agents safely.

Developing a New Hybrid Revascularization Program: a Road Map for Hospital Managers and Physician Leaders Journal of Interventional Cardiology. Dec, 2012 | Pubmed ID: 22861054 Hybrid coronary revascularization, which involves minimally invasive direct coronary artery bypass surgery using the left internal mammary artery to left anterior descending and percutaneous coronary intervention using drug-eluting stents for the remaining diseased coronary vessels, is an innovative approach to decrease the morbidity of conventional surgery. Little information is available to guide hospital managers and physician leaders in implementing a hybrid revascularization program. In this article, we describe the people-process-technology issues that managers and leaders are likely to encounter as they develop a hybrid revascularization program in their practice.

Systems Analysis of Transcription Factor Activities in Environments with Stable and Dynamic Oxygen Concentrations Open Biology. Jul, 2012 | Pubmed ID: 22870390 Understanding gene regulation requires knowledge of changes in transcription factor (TF) activities. Simultaneous direct measurement of numerous TF activities is currently impossible. Nevertheless, statistical approaches to infer TF activities have yielded non-trivial and verifiable predictions for individual TFs. Here, global statistical modelling identifies changes in TF activities from transcript profiles of Escherichia coli growing in stable (fixed oxygen availabilities) and dynamic (changing oxygen availability) environments. A core oxygen-responsive TF network, supplemented by additional TFs acting under specific conditions, was identified. The activities of the cytoplasmic oxygen-responsive TF, FNR, and the membrane-bound terminal oxidases implied that, even on the scale of the bacterial cell, spatial effects significantly influence oxygen-sensing. Several transcripts exhibited asymmetrical patterns of abundance in aerobic to anaerobic and anaerobic to aerobic transitions. One of these transcripts, ndh, encodes a major component of the aerobic respiratory chain and is regulated by oxygen-responsive TFs ArcA and FNR. Kinetic modelling indicated that ArcA and FNR behaviour could not explain the ndh transcript profile, leading to the identification of another TF, PdhR, as the source of the asymmetry. Thus, this approach illustrates how systematic examination of regulatory responses in stable and dynamic environments yields new mechanistic insights into adaptive processes.

The Ethical and Economic Impact of Defaults Seminars in Respiratory and Critical Care Medicine. Aug, 2012 | Pubmed ID: 22875385 Medical care offered to the critically ill often occurs by default, unfolding automatically unless concerted effort is made to do otherwise. In their scope, defaults include traditional approaches to treatment and decision making, as well as policies deliberately set to promote specific health outcomes. Defaults are ethically sound to the extent that they foster patient well-being and autonomy. Unfortunately in practice, some defaults lead to ineffective, unwanted, and expensive care. This article reviews the ethical and economic impact of defaults, paying special attention to their influence on the practice of cardiopulmonary resuscitation and admission to the intensive care unit.

Species Specific Differences in the in Vitro Metabolism of the Flame Retardant Mixture, FiremasterÂ® BZ-54 Aquatic Toxicology (Amsterdam, Netherlands). Nov, 2012 | Pubmed ID: 22889877 Firemaster(Â®) BZ-54 is a flame retardant additive and consists of a brominated benzoate (2-ethylhexyl 2,3,4,5-tetrabromobenzoate; TBB) and a brominated phthalate (bis (2-ethylhexyl) 2,3,4,5-tetrabromophthalate; TBPH). Previous research has shown that fathead minnows exposed in vivo to Firemaster(Â®) BZ-54 accumulate TBB and TBPH. This study examined the in vitro biotransformation potential of TBB and TBPH in hepatic subcellular fractions (i.e., S9, microsomes and cytosol) in the fathead minnow, common carp, mouse and snapping turtle. Metabolism was evaluated by measuring the loss of the parent TBB or TBPH and identifying potential metabolites in the sample extracts. Metabolic loss of TBPH was measured for all species, while TBB loss was observed for all species except for the snapping turtle. Several metabolites were observed in all of the incubations except for snapping turtle. Metabolites observed appeared to be derived from TBB, given their structures and lack of appearance in the snapping turtle incubations. One of these metabolites, 2,3,4,5-tetrabromomethylbenzoate has been identified for the first time in a biological system. When metabolized, TBB and TBPH loss was found in each subcellular fraction suggesting that the enzyme(s) involved are present in both soluble and membrane-bound forms. It can be concluded that a broad range of species are capable of metabolizing TBB and TBPH to various metabolites and further research should be carried out to ascertain the specific products formed from metabolism of TBB and TBPH.

Addressing Sexual and Relationship Violence in the LGBT Community Using a Bystander Framework Harvard Review of Psychiatry. Jul-Aug, 2012 | Pubmed ID: 22894729 Sexual and relationship violence are two major public health issues that affect an alarming number of undergraduate students. As a result, many colleges and universities have protocols to serve victims of these forms of violence. Despite federal legislation stating that all students should have equitable experiences, current protocols and programs focus primarily on heterosexual students. College student victims of sexual and relationship violence who identify as lesbian, gay, bisexual, or transgender can face particular challenges, including disclosure of their sexual and gender orientations, and revictimization when seeking services. In recent years an increasing number of campuses have adopted bystander prevention strategies to address sexual and relationship violence. These strategies seek to engage community members in the prevention of sexual and relationship violence by training them to identify and safely intervene in situations where sexual or relationship violence is about to occur, is occurring, or has occurred. In this article we review published bystander prevention strategies that focus on preventing sexual and relationship violence in the campus community, and discuss how bystander strategies are addressing or can address relationship and sexual violence in the LGBT community.

Evaluation of Two Multiplex Real-time PCR Screening Capabilities for the Detection of Bacillus Anthracis, Francisella Tularensis and Yersinia Pestis in Blood Samples Generated from Murine Infection Models Journal of Medical Microbiology. Nov, 2012 | Pubmed ID: 22899777 Two multiplex PCR screening capabilities (TaqMan Array Cards and FilmArray) were evaluated for their ability to detect Bacillus anthracis, Francisella tularensis and Yersinia pestis in blood samples obtained from respective murine infection models. Blood samples were obtained from infected mice at 24 h intervals after exposure. Multiplex PCR results were compared with standard blood culture and singleplex real-time PCR. Across all three models, 71 mice were tested in total, within which a subset of 43 samples was shown to contain an infecting agent by at least one of the detection technologies. Within this subset of positive samples, for each model studied, the detection rates of each technology were compared. The B. anthracis model blood culture (14 of 15 agent-containing samples tested) and FilmArray PCR (12 of 15) were shown to have equivalent detection rates, which were significantly higher (at the 95â€Š% confidence level) than singleplex (five of 14) or Array Card (two of 14) PCRs. The F. tularensis model blood culture (12 of 12) was shown to have a significantly higher (at 95â€Š% confidence level) detection rate than all PCR technologies, with FilmArray (seven of 11) and singleplex (seven of 12) PCRs shown to have significantly higher (at 95â€Š% confidence level) detection rates than the Array Card PCR (two of 11). Within the Y. pestis model, there was no significant difference in detection rates between blood culture (10 of 16), singleplex PCR (14 of 16), Array Card PCR (10 of 16) and FilmArray PCR (10 of 13).

GB Virus C Viremia is Associated with Higher Levels of Double-negative T Cells and Lower T-cell Activation in HIV-infected Individuals Receiving Antiretroviral Therapy The Journal of Infectious Diseases. Nov, 2012 | Pubmed ID: 22927453 Double-negative T cells (DNTCs; ie, CD3(+)CD4(-)CD8(-) T cells) play a role in limiting chronic immune activation. GB virus C (GBV-C) infection is associated with reduced T-cell activation in human immunodeficiency virus (HIV)-infected individuals. T-cell activation and DNTCs were measured in HIV-infected subjects with a nondetectable HIV load. GBV-C-viremic subjects had significantly reduced CD4(+) and CD8(+) T-cell activation (PÂ =Â .003 and .034, respectively) and significantly increased DNTCs (PÂ =Â .038), compared with nonviremic subjects. GBV-C load correlated with DNTC percentage (PÂ =Â .004). Thus, GBV-C infection is associated with an increase in DNTCs, which may contribute to reduced immune activation during HIV infection.

The Financial Repercussions of New Work-limiting Health Conditions for Older Workers Inquiry : a Journal of Medical Care Organization, Provision and Financing. 2012 | Pubmed ID: 22931021 This analysis used propensity score matching to construct a comparison sample that is observationally similar at baseline interview to older workers who later experience the onset of a medical condition that limits their ability to work. Using these matched onset and comparison samples, we studied trajectories in earnings and income around onset of the work limitation. Earnings two years after onset for the work-limitation group were 50% lower and poverty rates were nearly double. Income from unemployment insurance, workers' compensation, and retirement and disability benefits offset only a small amount of the earnings declines, resulting in decreased overall household income after onset of the work-limiting condition.

GB Virus C Infection is Associated with a Reduced Rate of Reactivation of Latent HIV and Protection Against Activation-induced T-cell Death Antiviral Therapy. 2012 | Pubmed ID: 22951385 GB virus C (GBV-C) coinfection is associated with reduced immune activation and a block in CD4(+) T-cell proliferation following interleukin-2 (IL-2) therapy in HIV-infected individuals. We examined peripheral blood mononuclear cells (PBMCs) from HIV-infected subjects with and without GBV-C viraemia to determine if GBV-C correlated with reactivation of latent HIV, T-cell proliferation or T-cell survival following in vitro activation with phytohaemagglutinin A and IL-2 (PHA/IL-2).

Research Methods and Statistical Techniques in Addiction Addiction (Abingdon, England). Oct, 2012 | Pubmed ID: 22962950

Escherichia Coli Isolates That Carry Vat, FyuA, ChuA, and YfcV Efficiently Colonize the Urinary Tract Infection and Immunity. Dec, 2012 | Pubmed ID: 22966046 Extraintestinal Escherichia coli (ExPEC), a heterogeneous group of pathogens, encompasses avian, neonatal meningitis, and uropathogenic E. coli strains. While several virulence factors are associated with ExPEC, there is no core set of virulence factors that can be used to definitively differentiate these pathotypes. Here we describe a multiplex of four virulence factor-encoding genes, yfcV, vat, fyuA, and chuA, highly associated with uropathogenic E. coli strains that can distinguish three groups of E. coli: diarrheagenic and animal-associated E. coli strains, human commensal and avian pathogenic E. coli strains, and uropathogenic and neonatal meningitis E. coli strains. Furthermore, human intestinal isolates that encode all four predictor genes express them during exponential growth in human urine and colonize the bladder in the mouse model of ascending urinary tract infection in higher numbers than human commensal strains that do not encode the four predictor genes (P = 0.02), suggesting that the presence of the predictors correlates with uropathogenic potential.

Relationship Between Hydrogen Sulfide Levels and HDL-cholesterol, Adiponectin, and Potassium Levels in the Blood of Healthy Subjects Atherosclerosis. Nov, 2012 | Pubmed ID: 22989474 Hydrogen sulfide (H(2)S) is an important signaling molecule whose blood levels have been shown to be lower in certain disease states. Increasing evidence indicates that H(2)S plays a potentially significant role in many biological processes and that malfunctioning of H(2)S homeostasis may contribute to the pathogenesis of vascular inflammation and atherosclerosis. This study examined the fasting blood levels of H(2)S, HDL-cholesterol, LDL-cholesterol, triglycerides, adiponectin, resistin, and potassium in 36 healthy adult volunteers. There was a significant positive correlation between blood levels of H(2)S and HDL-cholesterol (rÂ =Â 0.49, pÂ =Â 0.003), adiponectin (rÂ =Â 0.36, pÂ =Â 0.04), and potassium (rÂ =Â 0.34, pÂ =Â 0.047), as well as a significant negative correlation with LDL/HDL levels (rÂ =Â -0.39, pÂ =Â 0.02). This is the first demonstration of an association of circulating levels of H(2)S with the HDL, LDL, and adiponectin homeostasis in the blood of healthy humans.

Molecular Insights into Glycogen Î±-particle Formation Biomacromolecules. Nov, 2012 | Pubmed ID: 23004915 Glycogen, a hyperbranched complex glucose polymer, is an intracellular glucose store that provides energy for cellular functions, with liver glycogen involved in blood-glucose regulation. Liver glycogen comprises complex Î± particles made up of smaller Î² particles. The recent discovery that these Î± particles are smaller and fewer in diabetic, compared with healthy, mice highlights the need to elucidate the nature of Î±-particle formation; this paper tests various possibilities for binding within Î± particles. Acid hydrolysis effects, examined using dynamic light scattering and size exclusion chromatography, showed that the binding is not simple Î±-(1â†’4) or Î±-(1â†’6) glycosidic linkages. There was no significant change in Î± particle size after the addition of various reagents, which disrupt disulfide, protein, and hydrogen bonds and hydrophobic interactions. The results are consistent with proteinaceous binding between Î² particles in Î± particles, with the inability of protease to break apart particles being attributed to steric hindrance.

Measurement of the Proton-Air Cross Section at Sqrt[s]=57â€‰â€‰TeV with the Pierre Auger Observatory Physical Review Letters. Aug, 2012 | Pubmed ID: 23006259 We report a measurement of the proton-air cross section for particle production at the center-of-mass energy per nucleon of 57Â TeV. This is derived from the distribution of the depths of shower maxima observed with the Pierre Auger Observatory: systematic uncertainties are studied in detail. Analyzing the tail of the distribution of the shower maxima, a proton-air cross section of [505Â±22(stat)_{-36}^{+28}(syst)]â€‰â€‰mb is found.

Rodent Thyroid, Liver, and Fetal Testis Toxicity of the Monoester Metabolite of Bis-(2-ethylhexyl) Tetrabromophthalate (tbph), a Novel Brominated Flame Retardant Present in Indoor Dust Environmental Health Perspectives. Dec, 2012 | Pubmed ID: 23014847 Bis-(2-ethylhexyl) tetrabromophthalate (TBPH) is widely used as a replacement for polybrominated diphenyl ethers (PBDEs) in commercial flame retardant mixtures such as Firemaster 550. It is also used in a commercial mixture called DP 45. Mono-(2-ethyhexyl) tetrabromophthalate (TBMEHP) is a potentially toxic metabolite.

Single Fiber Analyses of Glycogen-related Proteins Reveal Their Differential Association with Glycogen in Rat Skeletal Muscle American Journal of Physiology. Cell Physiology. Dec, 2012 | Pubmed ID: 23015546 To understand how glycogen affects skeletal muscle physiology, we examined enzymes essential for muscle glycogen synthesis and degradation using single fibers from quiescent and stimulated rat skeletal muscle. Presenting a shift in paradigm, we show these proteins are differentially associated with glycogen granules. Protein diffusibility and/or abundance of glycogenin, glycogen branching enzyme (GBE), debranching enzyme (GDE), phosphorylase (GP), and synthase (GS) were examined in fibers isolated from rat fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscle. GDE and GP proteins were more abundant (~10- to 100-fold) in fibers from EDL compared with SOL muscle. GS and glycogenin proteins were similar between muscles while GBE had an approximately fourfold greater abundance in SOL muscle. Mechanically skinned fibers exposed to physiological buffer for 10 min showed ~70% total pools of GBE and GP were diffusible (nonbound), whereas GDE and GS were considerably less diffusible. Intense in vitro stimulation, sufficient to elicit a ~50% decrease in intracellular glycogen, increased diffusibility of GDE, GP, and GS (~15-60%) and decreased GBE diffusibility (~20%). Amylase treatment, which breaks Î±-1,4 linkages of glycogen, indicated differential diffusibilities and hence glycogen associations of GDE and GS. Membrane solubilization (1% Triton-X-100) allowed a small additional amount of GDE and GS to diffuse from fibers, suggesting the majority of nonglycogen-associated GDE/GS is associated with myofibrillar/contractile network of muscle rather than membranes. Given differences in enzymes required for glycogen metabolism, the current findings suggest glycogen particles have fiber-type-dependent structures. The greater catabolic potential of glycogen breakdown in fast-twitch fibers may account for different contraction induced rates of glycogen utilization.

Early Zebrafish Embryogenesis is Susceptible to Developmental TDCPP Exposure Environmental Health Perspectives. Nov, 2012 | Pubmed ID: 23017583 Chlorinated phosphate esters (CPEs) are widely used as additive flame retardants for low-density polyurethane foams and have frequently been detected at elevated concentrations within indoor environmental media.

American Pediatric Society 2012 Presidential Address: Mind the Gap Pediatric Research. Oct, 2012 | Pubmed ID: 23032510

Re-examination of Population Structure and Phylogeography of Hawksbill Turtles in the Wider Caribbean Using Longer MtDNA Sequences The Journal of Heredity. Nov-Dec, 2012 | Pubmed ID: 23045611 Management of the critically endangered hawksbill turtle in the Wider Caribbean (WC) has been hampered by knowledge gaps regarding stock structure. We carried out a comprehensive stock structure re-assessment of 11 WC hawksbill rookeries using longer mtDNA sequences, larger sample sizes (N = 647), and additional rookeries compared to previous surveys. Additional variation detected by 740 bp sequences between populations allowed us to differentiate populations such as Barbados-Windward and Guadeloupe (F (st) = 0.683, P < 0.05) that appeared genetically indistinguishable based on shorter 380 bp sequences. POWSIM analysis showed that longer sequences improved power to detect population structure and that when N < 30, increasing the variation detected was as effective in increasing power as increasing sample size. Geographic patterns of genetic variation suggest a model of periodic long-distance colonization coupled with region-wide dispersal and subsequent secondary contact within the WC. Mismatch analysis results for individual clades suggest a general population expansion in the WC following a historic bottleneck about 100 000-300 000 years ago. We estimated an effective female population size (N (ef)) of 6000-9000 for the WC, similar to the current estimated numbers of breeding females, highlighting the importance of these regional rookeries to maintaining genetic diversity in hawksbills. Our results provide a basis for standardizing future work to 740 bp sequence reads and establish a more complete baseline for determining stock boundaries in this migratory marine species. Finally, our findings illustrate the value of maintaining an archive of specimens for re-analysis as new markers become available.

PloS One. 2012 | Pubmed ID: 23071743

Maternal Serum Cholesterol Levels Are Elevated from the 1st Trimester of Pregnancy: a Cross-sectional Study Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. Nov, 2012 | Pubmed ID: 23075347 Cholesterol is monitored in the non-pregnant adult population, where normal values are established. Although reported to be elevated in pregnancy, cholesterol is neither routinely measured nor treated. We aimed to investigate cholesterol levels throughout pregnancy and to establish reference values for cholesterol in healthy pregnant women. This was a cross-sectional analysis of serum cholesterol in healthy women with an uncomplicated singleton pregnancy. Pregnant women attending for antenatal care were recruited and cholesterol levels assayed at 12, 20, 28 and 36 weeks' gestation and on day 1-3 postpartum. A total of 222 women were recruited. The majority (95%) were white Irish, with a median age of 31 years (range 16-46). Median BMI was 25.9 kg/m2 (range 18-40) and 16% were smokers. Cholesterol levels were elevated in all trimesters of pregnancy, with median values from 1st trimester raised outside the non-pregnant adult range. High-density lipoprotein (HDL) levels ranged from 0.9 to 3.7 mmol/l and low-density lipoprotein (LDL) levels ranged from 1.3 to 6.1 mmol/l. Fasting, smoking and obesity did not have any significant effects on results. Total and LDL-cholesterol levels were raised throughout pregnancy. Levels were above non-pregnant adult ranges as early as the 1st trimester. The implications of this on fetus and mother are undetermined and deserve further investigation.

Evaluation and Management of Geriatric Trauma: an Eastern Association for the Surgery of Trauma Practice Management Guideline The Journal of Trauma and Acute Care Surgery. Nov, 2012 | Pubmed ID: 23114492 Aging patients constitute an increasing proportion of patients treated at trauma centers. Previous and existing guidelines addressing care of the injured elder have not adequately addressed emerging data regarding optimal means for undertaking triage decisions, correcting coagulopathy, and the limitations of supraphysiologic resuscitation.

A Quantitative Map of the Liver Mitochondrial Phosphoproteome Reveals Posttranslational Control of Ketogenesis Cell Metabolism. Nov, 2012 | Pubmed ID: 23140645 Mitochondria are dynamic organelles that playÂ a central role in a diverse array of metabolic processes. Elucidating mitochondrial adaptations to changing metabolic demands and the pathogenic alterations that underlie metabolic disorders represent principal challenges in cell biology. Here, we performed multiplexed quantitative mass spectrometry-based proteomics to chart the remodeling of the mouse liver mitochondrial proteome and phosphoproteome during both acute and chronic physiological transformations in more than 50 mice. Our analyses reveal that reversible phosphorylation is widespread in mitochondria, and is a key mechanism for regulating ketogenesis during the onset of obesity and type 2 diabetes. Specifically, we have demonstrated that phosphorylation of a conserved serine on Hmgcs2 (S456) significantly enhances its catalytic activity in response to increased ketogenic demand. Collectively, our work describes the plasticity of this organelle at high resolution and provides a framework forÂ investigating the roles of proteome restructuringÂ and reversible phosphorylation in mitochondrial adaptation.

Sun Protection and Exposure Behaviors Among Hispanic Adults in the United States: Differences According to Acculturation and Among Hispanic Subgroups BMC Public Health. 2012 | Pubmed ID: 23153104 Skin cancer prevention interventions that target the growing number of U.S. Hispanics are lacking. The current study examined the prevalence and correlates of sun protection and exposure behaviors (i.e., sunscreen use, shade seeking, use of sun protective clothing, and sunburns) among U.S. Hispanics with sun sensitive skin, with a focus on potential differences according to acculturation and Hispanic origin.

Calcinosis Cutis Following Contact with Calcium Chloride Solution The Australasian Journal of Dermatology. Nov, 2012 | Pubmed ID: 23157788 Calcinosis cutis is the deposition of insoluble calcium in the cutaneous tissue. Calcinosis cutis can be classified as metastatic, dystrophic, idiopathic or exogenous. We report a 48-year-old white man who was dismantling a portable ice skating rink when calcium chloride solution from the pipes spilt onto his clothing. Several days later, he started to develop mildly pruritic erythematous papules, some studded with white deposits and some with umbilication over the exposed areas corresponding to the spillage of the calcium chloride solution. Histological features revealed interstitial fibrohistiocytic reaction with calcium-encrusted degenerated collagen bundles in the dermis which was further confirmed by von Kossa stain. He was commenced on topical corticosteroid cream twice daily and the lesions cleared completely between 6 to 10â€ƒweeks.

Exercise and Sport for Persons with Spinal Cord Injury PM & R : the Journal of Injury, Function, and Rehabilitation. Nov, 2012 | Pubmed ID: 23174556 This review article provides an overview of the evidence that links exercise and sports participation to physical and psychological well-being among people with spinal cord injury. Two aspects of physical well-being are examined, including the prevention of chronic disease and the promotion of physical fitness. Multiple aspects of psychosocial well-being are discussed, including mental health, social participation, and life satisfaction. The review concludes with future research recommendations and a discussion of challenges and opportunities for using exercise and sports to promote health and well-being among people living with spinal cord injury.

Novel and High Volume Use Flame Retardants in US Couches Reflective of the 2005 PentaBDE Phase Out Environmental Science & Technology. Dec, 2012 | Pubmed ID: 23186002 California's furniture flammability standard Technical Bulletin 117 (TB 117) is believed to be a major driver of chemical flame retardant (FR) use in residential furniture in the United States. With the phase-out of the polybrominated diphenyl ether (PBDE) FR mixture PentaBDE in 2005, alternative FRs are increasingly being used to meet TB 117; however, it was unclear which chemicals were being used and how frequently. To address this data gap, we collected and analyzed 102 samples of polyurethane foam from residential couches purchased in the United States from 1985 to 2010. Overall, we detected chemical flame retardants in 85% of the couches. In samples purchased prior to 2005 (n = 41) PBDEs associated with the PentaBDE mixture including BDEs 47, 99, and 100 (PentaBDE) were the most common FR detected (39%), followed by tris(1,3-dichloroisopropyl) phosphate (TDCPP; 24%), which is a suspected human carcinogen. In samples purchased in 2005 or later (n = 61) the most common FRs detected were TDCPP (52%) and components associated with the Firemaster550 (FM 550) mixture (18%). Since the 2005 phase-out of PentaBDE, the use of TDCPP increased significantly. In addition, a mixture of nonhalogenated organophosphate FRs that included triphenyl phosphate (TPP), tris(4-butylphenyl) phosphate (TBPP), and a mix of butylphenyl phosphate isomers were observed in 13% of the couch samples purchased in 2005 or later. Overall the prevalence of flame retardants (and PentaBDE) was higher in couches bought in California compared to elsewhere, although the difference was not quite significant (p = 0.054 for PentaBDE). The difference was greater before 2005 than after, suggesting that TB 117 is becoming a de facto standard across the U.S. We determined that the presence of a TB 117 label did predict the presence of a FR; however, lack of a label did not predict the absence of a flame retardant. Following the PentaBDE phase out, we also found an increased number of flame retardants on the market. Given these results, and the potential for human exposure to FRs, health studies should be conducted on the types of FRs identified here.

Impairment of Coronary Arteriolar Endothelium-dependent Dilation After Multi-walled Carbon Nanotube Inhalation: a Time-course Study International Journal of Molecular Sciences. 2012 | Pubmed ID: 23203034 Engineered nanomaterials have been developed for widespread applications due to many highly unique and desirable characteristics. The purpose of this study was to assess pulmonary inflammation and subepicardial arteriolar reactivity in response to multi-walled carbon nanotube (MWCNT) inhalation and evaluate the time course of vascular alterations. Rats were exposed to MWCNT aerosols producing pulmonary deposition. Pulmonary inflammation via bronchoalveolar lavage and MWCNT translocation from the lungs to systemic organs was evident 24 h post-inhalation. Coronary arterioles were evaluated 24-168 h post-exposure to determine microvascular response to changes in transmural pressure, endothelium-dependent and -independent reactivity. Myogenic responsiveness, vascular smooth muscle reactivity to nitric oxide, and Î±-adrenergic responses all remained intact. However, a severe impact on endothelium-dependent dilation was observed within 24 h after MWCNT inhalation, a condition which improved, but did not fully return to control after 168 h. In conclusion, results indicate that MWCNT inhalation not only leads to pulmonary inflammation and cytotoxicity at low lung burdens, but also a low level of particle translocation to systemic organs. MWCNT inhalation also leads to impairments of endothelium-dependent dilation in the coronary microcirculation within 24 h, a condition which does not fully dissipate within 168 h. The innovations within the field of nanotechnology, while exciting and novel, can only reach their full potential if toxicity is first properly assessed.

GB Virus C Infection is Associated with Altered Lymphocyte Subset Distribution and Reduced T Cell Activation and Proliferation in HIV-infected Individuals PloS One. 2012 | Pubmed ID: 23209780 GBV-C infection is associated with prolonged survival and with reduced T cell activation in HIV-infected subjects not receiving combination antiretroviral therapy (cART). The relationship between GBV-C and T cell activation in HIV-infected subjects was examined. HIV-infected subjects on cART with non-detectable HIV viral load (VL) or cART naÃ¯ve subjects were studied. GBV-C VL and HIV VL were determined. Cell surface markers of activation (CD38(+)/HLA-DR(+)), proliferation (Ki-67+), and HIV entry co-receptor expression (CCR5+ and CXCR4+) on total CD4+ and CD8+ T cells, and on naÃ¯ve, central memory (CM), effector memory (EM), and effector CD4+ and CD8+ subpopulations were measured by flow cytometry. In subjects with suppressed HIV VL, GBV-C was consistently associated with reduced activation in naÃ¯ve, CM, EM, and effector CD4+ cells. GBV-C was associated with reduced CD4+ and CD8+ T cell surface expression of activation and proliferation markers, independent of HIV VL classification. GBV-C was also associated with higher proportions of naÃ¯ve CD4+ and CD8+ T cells, and with lower proportions of EM CD4+ and CD8+ T cells. In conclusion, GBV-C infection was associated with reduced activation of CD4+ and CD8+ T cells in both HIV viremic and HIV RNA suppressed patients. Those with GBV-C infection demonstrated an increased proportion of naive T cells and a reduction in T cell activation and proliferation independent of HIV VL classification, including those with suppressed HIV VL on cART. Since HIV pathogenesis is thought to be accelerated by T cell activation, these results may contribute to prolonged survival among HIV infected individuals co-infected with GBV-C. Furthermore, since cART therapy does not reduce T cell activation to levels seen in HIV-uninfected people, GBV-C infection may be beneficial for HIV-related diseases in those effectively treated with anti-HIV therapy.

Overweight and Obesity in Pregnancy: the Evidence-practice Gap in Staff Knowledge, Attitudes and Practices The Australian & New Zealand Journal of Obstetrics & Gynaecology. Dec, 2012 | Pubmed ID: 23216325 Statewide (Queensland) Clinical Guidelines reflecting current best practice have recently become available for the management of pregnancy-related obesity. However, dissemination of guidelines alone do not change practice.

A New Anti-fibrotic Drug Attenuates Cardiac Remodeling and Systolic Dysfunction Following Experimental Myocardial Infarction International Journal of Cardiology. Dec, 2012 | Pubmed ID: 23219315 BACKGROUND: Pathological deposition of extracellular matrix in the non-infarct zone (NIZ) of the ventricle post myocardial infarction (MI) is a key contributor to cardiac remodeling and heart failure. FT011, a novel antifibrotic compound, was evaluated for its efficacy in neonatal cardiac fibroblasts (NCF) and in an experimental MI model. METHODS AND RESULTS: Collagen synthesis in NCF was determined by (3)H-proline incorporation following stimulation with TGF-Î² or angiotensin II (Ang II). FT011 inhibited collagen synthesis to both agents in a dose dependent manner. In vivo, Sprague Dawley rats underwent left anterior descending coronary artery ligation or sham surgery and were randomized one week later to receive either FT011 (200mg/kg/day) or vehicle for a further 4weeks. Echocardiography and cardiac catheterization were performed, and tissues were collected for histological analysis of collagen, myocyte hypertrophy, interstitial macrophage accumulation and Smad2 phosphorylation. mRNA expression of collagens I and III and TGF-Î² was measured using in situ hybridization and RT-PCR, respectively. FT011 treatment was associated with improved cardiac function (increased ejection fraction, fraction shortening and preload recruitable stroke work) and myocardial remodeling (reduced left ventricular diameter and volume at both end diastolic and systolic) compared with vehicle treatment. FT011 significantly reduced collagen matrix deposition, myocyte hypertrophy and interstitial macrophage infiltration, and mRNA expression of collagens I and III in NIZ compared with vehicle treatment. CONCLUSION: Anti-fibrotic therapy with FT011 in MI rats attenuated fibrosis and preserved systolic function.

Deep Clonal Profiling of Formalin Fixed Paraffin Embedded Clinical Samples PloS One. 2012 | Pubmed ID: 23226320 Formalin fixed paraffin embedded (FFPE) tissues are a vast resource of annotated clinical samples. As such, they represent highly desirable and informative materials for the application of high definition genomics for improved patient management and to advance the development of personalized therapeutics. However, a limitation of FFPE tissues is the variable quality of DNA extracted for analyses. Furthermore, admixtures of non-tumor and polyclonal neoplastic cell populations limit the number of biopsies that can be studied and make it difficult to define cancer genomes in patient samples. To exploit these valuable tissues we applied flow cytometry-based methods to isolate pure populations of tumor cell nuclei from FFPE tissues and developed a methodology compatible with oligonucleotide array CGH and whole exome sequencing analyses. These were used to profile a variety of tumors (breast, brain, bladder, ovarian and pancreas) including the genomes and exomes of matching fresh frozen and FFPE pancreatic adenocarcinoma samples.

The Murri Clinic: a Comparative Retrospective Study of an Antenatal Clinic Developed for Aboriginal and Torres Strait Islander Women BMC Pregnancy and Childbirth. 2012 | Pubmed ID: 23256901 Indigenous Australians are a small, widely dispersed population. Regarding childbearing women and infants, inequities in service delivery and culturally unsafe services contribute to significantly poorer outcomes, with a lack of high-level research to guide service redesign. This paper reports on an Evaluation of a specialist (Murri) antenatal clinic for Australian Aboriginal and Torres Strait Islander women.

The Routine Use of Tranexamic Acid in Hip and Knee Replacements Bulletin of the NYU Hospital for Joint Diseases. 2012 | Pubmed ID: 23267449 Our aim was to determine whether the administration of intravenous tranexamic acid is a safe and effective means of reducing blood loss associated with hip and knee replacement surgery.

Cardiac Catheterisation of Patients with Common Arterial Trunk and Transposition of the Great Arteries Cardiology in the Young. Dec, 2012 | Pubmed ID: 23331588 Cardiac catheterisation continues to play an important role in the long-term management of patients with common arterial trunk and transposition of the great arteries. Although non-invasive imaging has largely eliminated the need for diagnostic catheterisation in newborns with these congenital cardiac lesions, cardiac catheterisation is an important tool for the diagnosis of a variety of problems encountered after surgical intervention, and allows interventions to be performed when feasible. We review the indications for cardiac catheterisation and describe the specifics for various interventional procedures for these patients in this manuscript.

Chemically Modified Oligonucleotides Modulate an Epigenetically Varied and Transient Form of Transcription Silencing of HIV-1 in Human Cells Molecular Therapy. Nucleic Acids. 2012 | Pubmed ID: 23343927 Small noncoding RNAs (ncRNAs) have been shown to guide epigenetic silencing complexes to target loci in human cells. When targeted to gene promoters, these small RNAs can lead to long-term stable epigenetic silencing of gene transcription. To date, small RNAs have been shown to modulate transcriptional gene silencing (TGS) of human immunodeficiency virus type 1 (HIV-1) as well as several other disease-related genes, but it has remained unknown as to what extent particular chemistries can be used to generate single-stranded backbone-modified oligonucleotides that are amenable to this form of gene targeting and regulation. Here, we present data indicating that specific combinations of backbone modifications can be used to generate single-stranded antisense oligonucleotides that can functionally direct TGS of HIV-1 in a manner that is however, independent of epigenetic changes at the target loci. Furthermore, this functionality appears contingent on the absence of a 5' phosphate in the oligonucleotide. These data suggest that chemically modified oligonucleotide based approaches could be implemented as a means to regulate gene transcription in an epigenetically independent manner.

Feedback Control of Protein Expression in Mammalian Cells by Tunable Synthetic Translational Inhibition ACS Synthetic Biology. Mar, 2012 | Pubmed ID: 23651072 Feedback regulation plays a crucial role in dynamic gene expression in nature, but synthetic translational feedback systems have yet to be demonstrated. Here we use an RNA/protein interaction-based synthetic translational switch to create a feedback system that tightly controls the expression of proteins of interest in mammalian cells. Feedback is mediated by modified ribosomal L7Ae proteins, which bind a set of RNA motifs with a range of affinities. We designed these motifs into L7Ae-encoding mRNA. Newly translated L7Ae binds its own mRNA, inhibiting further translation. This inhibition tightly feedback-regulates the concentration of L7Ae and any fusion partner of interest. A mathematical model predicts system behavior as a function of RNA/protein affinity. We further demonstrate that the L7Ae protein can simultaneously and tunably regulate the expression of multiple proteins of interest by binding RNA control motifs built into each mRNA, allowing control over the coordinated expression of protein networks.

Associations Between Serum Levels of Polybrominated Diphenyl Ether (PBDE) Flame Retardants and Environmental and Behavioral Factors in Pregnant Women Journal of Exposure Science & Environmental Epidemiology. Mar, 2013 | Pubmed ID: 22760441 Polybrominated diphenyl ethers (PBDE) are flame retardants that were previously used in upholstery, fabrics, and household appliances. PBDEs have been linked to adverse health outcomes, including neurotoxicity, thyroid hormone dysregulation, endocrine disruption, and poor semen quality. Because PBDEs pass into placental circulation, maternal exposures can approximate fetal exposures. Our objectives were to determine whether diet and specific human behaviors were significantly associated with PBDE exposures in a cohort of pregnant women. Women between the 34th and 38th week of pregnancy were given a questionnaire about behavioral, environmental, and dietary factors and asked to provide blood samples. Serum PBDE levels were measured using GS-MS and lipid adjusted. An adjusted ordinary least squares regression model was run to identify potential associations between behaviors and serum PBDE levels. Serum concentrations of BDEs 47, 99, 100, and 153 were found above the limit of detection in at least 50% of study participants and used in our models. Associations with serum PBDEs were observed with self-reported hand-to-mouth behaviors, including biting nails and licking fingers. Serum BDE levels of 47, 99, 153, and total PBDEs were also significantly higher in those individuals owning a large-screen TV compared with those who did not. Serum PBDE levels were comparable to levels reported in the general population. Hand-to-mouth behaviors may influence serum PBDE concentrations in adults. Household electronics such as large-screen TVs appear to serve as a significant source of PBDEs in pregnant women. Together, hand-to-mouth behaviors and TV ownership may serve as a route of exposure to PBDEs in adults.

Comparison of a Single Vs. a Four Intradermal Sterile Water Injection for Relief of Lower Back Pain for Women in Labour: a Randomised Controlled Trial Midwifery. Jun, 2013 | Pubmed ID: 22770818 sterile water injections are a simple, safe, effective, non-pharmacological technique for relieving back pain in labour, however the number of injections required to achieve optimal analgesia is unknown. The objective of this trial was to evaluate the degree and duration of analgesia provided by a single injection of sterile water, compared to four injections.

Air Pollution Particulate Matter Collected from an Appalachian Mountaintop Mining Site Induces Microvascular Dysfunction Microcirculation (New York, N.Y. : 1994). Feb, 2013 | Pubmed ID: 22963349 Air pollution PM is associated with cardiovascular morbidity and mortality. In Appalachia, PM from mining may represent a health burden to this sensitive population that leads the nation in cardiovascular disease, among others. Cardiovascular consequences following inhalation of PM(MTM) are unclear, but must be identified to establish causal effects.

Clinical and Microbiologic Features Guiding Treatment Recommendations for Brain Abscesses in Children The Pediatric Infectious Disease Journal. Feb, 2013 | Pubmed ID: 23001027 There are no guidelines for the management of brain abscesses in children, and there is a paucity of recent data describing clinical and microbiologic features. We aimed to identify factors affecting outcome to inform antibiotic recommendations.

Cranberry-containing Products Are Associated with a Protective Effect Against Urinary Tract Infections Evidence-based Medicine. Jun, 2013 | Pubmed ID: 23125232

Accumulation and Endocrine Disrupting Effects of the Flame Retardant Mixture FiremasterÂ® 550 in Rats: an Exploratory Assessment Journal of Biochemical and Molecular Toxicology. Feb, 2013 | Pubmed ID: 23139171 FiremasterÂ® 550 (FM 550), a fire-retardant mixture used in foam-based products, was recently identified as a common contaminant in household dust. The chemical structures of its principle components suggest they have endocrine disrupting activity, but nothing is known about their physiological effects at environmentally relevant exposure levels. The goal of this exploratory study was to evaluate accumulation, metabolism and endocrine disrupting effects of FM 550 in rats exposed to 100 or 1000 Âµg/day across gestation and lactation. FM 550 components accumulated in tissues of exposed dams and offspring and induced phenotypic hallmarks associated with metabolic syndrome in the offspring. Effects included increased serum thyroxine levels and reduced hepatic carboxylesterease activity in dams, and advanced female puberty, weight gain, male cardiac hypertrophy, and altered exploratory behaviors in offspring. Results of this study are the first to implicate FM 550 as an endocrine disruptor and an obesogen at environmentally relevant levels.

A Framework for Creating and Evaluating Competencies for Emergency Nurses Journal of Emergency Nursing: JEN : Official Publication of the Emergency Department Nurses Association. May, 2013 | Pubmed ID: 23142098

Diabetic Calcaneal Fractures Clinics in Podiatric Medicine and Surgery. Jan, 2013 | Pubmed ID: 23164444 Calcaneal fractures among the diabetic population are severe and complex injuries that warrant careful evaluation in an effort to carry out adequate conservative or surgical management. The complication rates associated with diabetic fracture management are increased and may include poor wound healing, deep infection, malunion, and Charcot neuroarthropathy, each of which can pose a risk for limb loss. The significant surgery-associated morbidity accompanying diabetic calcaneal fractures has led to improved methods of calcaneal fracture management. This article reviews the overall management of diabetic calcaneal fractures, complications, and outcomes.

The Epidemiology of Microbial Keratitis with Silicone Hydrogel Contact Lenses Eye & Contact Lens. Jan, 2013 | Pubmed ID: 23172318 It was widely anticipated that after the introduction of silicone hydrogel lenses, the risk of microbial keratitis would be lower than with hydrogel lenses because of the reduction in hypoxic effects on the corneal epithelium. Large-scale epidemiological studies have confirmed that the absolute and relative risk of microbial keratitis is unchanged with overnight use of silicone hydrogel materials. The key findings include the following: (1) The risk of infection with 30 nights of silicone hydrogel use is equivalent to 6 nights of hydrogel extended wear; (2) Occasional overnight lens use is associated with a greater risk than daily lens use; (3) The rate of vision loss due to corneal infection with silicone hydrogel contact lenses is similar to that seen in hydrogel lenses; (4) The spectrum of causative organisms is similar to that seen in hydrogel lenses, and the material type does not impact the corneal location of presumed microbial keratitis; and (5) Modifiable risk factors for infection include overnight lens use, the degree of exposure, failing to wash hands before lens handling, and storage case hygiene practice. The lack of change in the absolute risk of disease would suggest that exposure to large number of pathogenic organisms can overcome any advantages obtained from eliminating the hypoxic effects of contact lenses. Epidemiological studies remain important in the assessment of new materials and modalities. Consideration of an early adopter effect with studies involving new materials and modalities and further investigation of the impact of second-generation silicone hydrogel materials is warranted.

Skin Cancer Surveillance Behaviors Among US Hispanic Adults Journal of the American Academy of Dermatology. Apr, 2013 | Pubmed ID: 23182066 Little skin cancer prevention research has focused on the US Hispanic population.

Effect of Human Skin Grafts on Whole-body Heat Loss During Exercise Heat Stress: a Case Report Journal of Burn Care & Research : Official Publication of the American Burn Association. Jul-Aug, 2013 | Pubmed ID: 23202874 When exposed to heat stress, increases in cutaneous blood flow and sweating in well-healed grafted skin are severely attenuated, which could impair whole-body heat loss if skin grafts cover a large portion of total body surface area (TBSA). It is unknown to what extent whole-body heat loss is impaired when skin grafts cover a significant (eg, >50%) proportion of TBSA. The authors examined whole-body heat exchange during and after 60 min of cycling exercise in the heat (35Â°C; 25% relative humidity), at a fixed rate of metabolic heat production (~400 W) in a woman (age, 36 years; mass, 78.2 kg) with well-healed (17+ years) skin grafts covering 75% of TBSA. Her responses were compared with two noninjured control subjects. Whole-body evaporative and dry heat exchange were measured by direct calorimetry. While exercising in the same ambient conditions and at the same rate of heat production, relative evaporative heat loss of nongrafted skin in the grafted subject (ie, evaporative heat loss per m) was nearly twice that of the control subjects. However, total rate of evaporative heat loss reached only 59% of the amount required for heat balance in the skin-grafted subject compared with 92 Â± 3% in controls. Thus, the increase in core temperature was 2-fold greater for the grafted (1.22Â°C) vs control (0.61 Â± 0.19Â°C) individuals. This case study demonstrates that a large area of grafted skin greatly diminishes maximum evaporative heat loss during exercise in the heat, making a compensable environment for control subjects uncompensable for skin-grafted individuals.

Attenuation of Armanni-Ebstein Lesions in a Rat Model of Diabetes by a New Anti-fibrotic, Anti-inflammatory Agent, FT011 Diabetologia. Mar, 2013 | Pubmed ID: 23242170 A key morphological feature of diabetic nephropathy is the accumulation and deposition of glycogen in renal tubular cells, known as Armanni-Ebstein lesions. While this observation has been consistently reported for many years, the molecular basis of these lesions remains unclear.

Pediatric Microcystic Meningioma: a Clinical, Histological, and Radiographic Case-based Review Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery. Mar, 2013 | Pubmed ID: 23250249 Microcystic meningioma (MM) is a World Health Organization grade I tumor that is rare in the pediatric population. Meningiomas account for approximately 2-4Â % of all childhood central nervous system (CNS) tumors compared to approximately 20Â % of all adult CNS tumors. The authors present one of the few confirmed cases of microcystic meningioma in a child and discuss the characteristic radiographic appearance and histological findings.

Silicone Hydrogel Lens-solution Interaction and Inflammation Eye & Contact Lens. Jan, 2013 | Pubmed ID: 23271475 Daily wear of silicone hydrogel (SiHy) lenses using marketed lens care solutions results in varied levels of anterior eye inflammation. There are several pathways that may lead to corneal and conjunctival inflammation that include mechanical, allergic, and pathogen driven stimuli. The hypotheses and evidence for these various models of inflammation will be discussed in the context of SiHy lens designs and materials and lens care solution components.

An Agenda for Children for the 113th Congress: Recommendations from the Pediatric Academic Societies Pediatrics. Jan, 2013 | Pubmed ID: 23277316 The 113th Congress of the United States begins in January 2013. With each new Congress, there are many changes, not only in the faces of the newly elected, but also in the membership of committees and the staff serving the members. As agendas for the session are set, there is a resurgence of conflicting priorities. In the past, when these conflicts were resolved, children were rarely at the top of the list. Given the numerous pressing national issues, both domestic and foreign, the same trend will likely occur.

Chimpanzee GB Virus C and GB Virus A E2 Envelope Glycoproteins Contain a Peptide Motif That Inhibits Human Immunodeficiency Virus Type 1 Replication in Human CD4âº T-cells The Journal of General Virology. Apr, 2013 | Pubmed ID: 23288422 GB virus type C (GBV-C) is a lymphotropic virus that can cause persistent infection in humans. GBV-C is not associated with any disease, but is associated with reduced mortality in human immunodeficiency virus type 1 (HIV-1)-infected individuals. Related viruses have been isolated from chimpanzees (GBV-Ccpz) and from New World primates (GB virus type A, GBV-A). These viruses are also capable of establishing persistent infection. We determined the nucleotide sequence encoding the envelope glycoprotein (E2) of two GBV-Ccpz isolates obtained from the sera of captive chimpanzees. The deduced GBV-Ccpz E2 protein differed from human GBV-C by 31â€Š% at the amino acid level. Similar to human GBV-C E2, expression of GBV-Ccpz E2 in a tet-off human CD4(+) Jurkat T-cell line significantly inhibited the replication of diverse HIV-1 isolates. This anti-HIV-replication effect of GBV-Ccpz E2 protein was reversed by maintaining cells in doxycycline to reduce E2 expression. Previously, we found a 17 aa region within human GBV-C E2 that was sufficient to inhibit HIV-1. Although GBV-Ccpz E2 differed by 3 aa differences in this region, the chimpanzee GBV-C 17mer E2 peptide inhibited HIV-1 replication. Similarly, the GBV-A peptide that aligns with this GBV-C E2 region inhibited HIV-1 replication despite sharing only 5 aa with the human GBV-C E2 sequence. Thus, despite amino acid differences, the peptide region on both the GBV-Ccpz and the GBV-A E2 protein inhibit HIV-1 replication similar to human GBV-C. Consequently, GBV-Ccpz or GBV-A infection of non-human primates may provide an animal model to study GB virus-HIV interactions.

3D Image-guided Robotic Needle Positioning System for Small Animal Interventions Medical Physics. Jan, 2013 | Pubmed ID: 23298100 This paper presents the design of a micro-CT guided small animal robotic needle positioning system. In order to simplify the robotic design and maintain a small targeting error, a novel implementation of the remote center of motion is used in the system. The system has been developed with the objective of achieving a mean targeting error of

Associations Between Brominated Flame Retardants in House Dust and Hormone Levels in Men The Science of the Total Environment. Feb, 2013 | Pubmed ID: 23333513 Brominated flame retardants (BFRs) are used in the manufacture of a variety of materials and consumer products in order to meet fire safety standards. BFRs may persist in the environment and have been detected in wildlife, humans and indoor dust and air. Some BFRs have demonstrated endocrine and reproductive effects in animals, but human studies are limited. In this exploratory study, we measured serum hormone levels and flame retardant concentrations [31 polybrominated diphenyl ether (PBDE) congeners and 6 alternate flame retardants] in house dust from men recruited through a US infertility clinic. PBDE congeners in dust were grouped by commercial mixtures (i.e. penta-, octa- and deca-BDE). In multivariable linear regression models adjusted by age and body mass index (BMI), significant positive associations were found between house dust concentrations of pentaBDEs and serum levels of free T4, total T3, estradiol, and sex hormone binding globulin (SHBG), along with an inverse association with follicle stimulating hormone (FSH). There were also positive associations of octaBDE concentrations with serum free T4, thyroid stimulating hormone (TSH), luteinizing hormone (LH) and testosterone and an inverse association of decaBDE concentrations with testosterone. Hexabromocyclododecane (HBCD) was associated with decreased SHBG and increased free androgen index. Dust concentrations of bis-tribromophenoxyethane (BTBPE) and tetrabromo-diethylhexylphthalate (TBPH) were positively associated with total T3. These findings are consistent with our previous report of associations between PBDEs (BDE 47, 99 and 100) in house dust and hormone levels in men, and further suggest that exposure to contaminants in indoor dust may be leading to endocrine disruption in men.

Positive Effects of Short Course Androgen Therapy on the Neurodevelopmental Outcome in Boys with 47,XXY Syndrome at 36 and 72 Months of Age American Journal of Medical Genetics. Part A. Mar, 2013 | Pubmed ID: 23345253 The effects of early androgen treatment on neurodevelopmental performance in pre-pubertal boys with 47,XXY have not been well investigated. The influence of hormones on brain development in humans suggests that a positive effect on neurodevelopmental outcome in young boys with XXY may be plausible with hormone replacement therapy. The aim of the study was to investigate retrospectively if an early course of androgen treatment (three injections of testosterone enanthate, 25 mg, each) had an impact on specific domains of neurodevelopmental function in boys with 47,XXY at 36 and 72 months of age. One hundred one boys with a karyotype of 47,XXY had neurodevelopmental assessments. The retrospective chart review resulted in one group (n = 34) who had received androgen treatment during infancy and the second group was untreated (N = 67). Statistical analysis was completed to determine if there was a positive effect from treatment observed at 36 and at 72 months on multiple domains of development. There were significant differences in multiple cognitive domains in the group who received androgen treatment, including multiple measures of language, intellectual, and neuromotor skills. Improved function was observed in neurodevelopmental outcome in boys with 47,XXY at 36 and 72 months who had been treated with a short course of androgen treatment in infancy. Continued research is underway to expand our understanding of the relationship of androgen, brain function, and neurobehavioral and neurodevelopmental outcome in boys with 47,XXY.

3. Ocular Surface Health with Contact Lens Wear Contact Lens & Anterior Eye : the Journal of the British Contact Lens Association. Jan, 2013 | Pubmed ID: 23347571 Eye care practitioners (ECPs) would tend to agree that wearing contact lenses increases the risk for infection, but millions of patients are still fitted with lenses every year because ECPs feel that the risk is manageable and that their patients' eye health can be protected. The Fusarium and Acanthamoeba keratitis outbreaks of years past were a wake-up call to manufacturers, ECPs, and regulatory agencies that risk cannot be managed without diligence, and that the complex relationship between contact lens materials, contact lens solutions, and compliance needs to be better understood in order to optimize the efficacy of contact lens care and improve care guidelines.

4. Contemporary Research in Contact Lens Care Contact Lens & Anterior Eye : the Journal of the British Contact Lens Association. Jan, 2013 | Pubmed ID: 23347572 As our understanding of the eye and how it works evolves, we must re-evaluate previous findings, beliefs, and methods of diagnosis and treatment. The eye has proven to be naturally adept at protecting itself from pathogenic intruders, but contact lens wear and lens cleaning products can adversely impact this innate ability. Keeping up to date on the latest information is challenging, and becomes more complex when trying to incorporate the new scientific data into clinical practice. Several factors prevent drawing a straight line from study findings to real-world results, such as patient compliance and potentially flawed diagnostic tools. In this section, we review the latest research findings and opinions related to contact lens care and further explore compliance and its effect on ocular health.

The Potential Impact of Washing Machines on Laundry Malodour Generation Letters in Applied Microbiology. Apr, 2013 | Pubmed ID: 23350695 A multidisciplinary approach has been adopted to investigate and identify the source of malodour in washing machines and the potential for cross-contamination of laundry. Four washing machines were olfactively graded, and the number of colony-forming units (CFUs) bacteria was determined in four specific locations. Then, samples of terry-towel and fleece were washed, without the use of detergent, in the machines, and the occurrence of malodour over a 52-h period was assessed. Analysis of the scrapings from the four locations in the two malodorous machines identified a plethora of volatile organic compounds (VOCs) by either olfactory detection or mass spectral identification post-gas chromatographic separation. In addition, microbiological analysis from the swabs from the four locations within all four washing machines was carried out. Quantitative analysis of VOCs from 66 microbiological isolates from either the washing machines or fabrics was carried out. In total, 10 VOCs were identified: dimethyl disulfide, 3-methyl-1-butanol, 2,4-dithiapentane, dimethyl trisulfide, 2-tridecanone, indole, 2-phenylethanol, isovaleric acid, isobutyric acid and 1-undecene.

Is It All the X: Familial Learning Dysfunction and the Impact of Behavioral Aspects of the Phenotypic Presentation of XXY? American Journal of Medical Genetics. Part C, Seminars in Medical Genetics. Feb, 2013 | Pubmed ID: 23359595 The behavioral phenotype of children with XXY has not been extensively studied until recently and this research has been confounded by insufficient study populations and ascertainment biases. The aim of the study was to expand the behavioral aspect of the XXY phenotype as well as investigate the role of existing familial learning disabilities (FLD) on behavioral problems. Behavioral phenotype of XXY includes social anxiety, ADHD, social communication, and atypical peer interactions. The Child Behavior Checklist (CBCL), Social Responsiveness Scale (SRS), and Gilliam Autism Rating Scale (GARS) were completed by the parents of 54 boys with XXY who had not received hormonal replacement prior to participation. Our findings suggest fewer behavioral deficits and lower severity in the general 47,XXY population than previously published and found significant differences between the groups with a positive FLD on the behavioral assessments. Findings demonstrate that boys with FLD exhibit an increased incidence and severity of behavioral problems. Our study expands on the findings of Samango-Sprouse et al. [Samango-Sprouse et al. (2012b) J Intellect Disabil Res] and the significant influence that FLD has on not only neurodevelopment, but also behavioral deficits. Our study suggests that part of the XXY phenotypic profile may be modulated by FLD. Further study is underway to examine the interaction between the many salient factors effecting behavioral and neurodevelopmental progression in XXY and variant forms. Â© 2013 Wiley Periodicals, Inc.

Musculoskeletal Anomalies in a Large Cohort of Boys with 49, XXXXY American Journal of Medical Genetics. Part C, Seminars in Medical Genetics. Feb, 2013 | Pubmed ID: 23359596 49, XXXXY is a rare aneuploidy and variant of Klinefelter syndrome, occurring in 1 per 80,000-100,000 live births. We present a cohort of 40 affected males, focusing on musculoskeletal problems. Subjects were participants in an annual 49er family support group meeting. Children were examined in a multidisciplinary clinic by a pediatric neurologist and geneticist, a pediatric orthopedist, a neurodevelopmentalist, and two physical therapists. The patient data were collected from this clinic from 2004 to 2012. All patients were required to have karyotypes that confirmed the presence of XXXXY. There was a high prevalence of musculoskeletal disorders, particularly hypotonia (34 patients [85%]), radioulnar synostosis (30 [75%]), pes planus (26 [65%]), asymmetric hip rotation (27 [67.5%]), and clinodactyly (24 [60%]). Other, less common lower-extremity disorders, included, 5 patients (12.5%) with unilateral club foot, 5 boys (12.5%) with pes cavus, 10 patients (25%) genu valgum and 2 children with genu varus (5%). To our knowledge, this is the first large cohort of boys with 49, XXXXY that focuses on musculoskeletal disorders. There was an increased incidence of hypotonia, clubfoot, avascular necrosis of the femoral head, radioulnar synostosis, and pes planus compared to the normative population. Boys with 49, XXXXY would benefit from multidisciplinary evaluations, particularly from pediatric orthopedists, physical therapists, neurologists, and geneticists for appropriate medical care.

Still a Man's World, but Why? Critical Care (London, England). Jan, 2013 | Pubmed ID: 23360580 ABSTRACT: Women are generally under-represented in many academic medical settings. Through a brief commentary on this issue, the present article discusses possible explanations for this under-representation as well as potential solutions. Issues examined include women in leadership positions, attrition out of academic medicine, salary imbalance between men and women, potential bias among both genders, and the need for cultural change. We believe this is an extremely important issue of which we all need to be aware and hope that articles such as this will aid in starting a crucial conversation about gender issues in academic medicine.

Outcomes of Care in Birth Centers: Demonstration of a Durable Model Journal of Midwifery & Women's Health. Jan-Feb, 2013 | Pubmed ID: 23363029 The safety and effectiveness of birth center care have been demonstrated in previous studies, including the National Birth Center Study and the San Diego Birth Center Study. This study examines outcomes of birth center care in the present maternity care environment.

Is Whole-body Thermoregulatory Function Impaired in Type 1 Diabetes Mellitus? Current Diabetes Reviews. Mar, 2013 | Pubmed ID: 23363333 During periods of extreme heat individuals with diabetes have greater rates of heat-related morbidity and mortality compared to their non-diabetic counterparts. The reason for this discrepancy is currently unknown. Furthermore, there is a lack of information about whether or not individuals with type 1 diabetes are at a thermoregulatory disadvantage during strenuous physical activity especially when performed in the heat.

Aryl Phosphate Esters Within a Major PentaBDE Replacement Product Induce Cardiotoxicity in Developing Zebrafish Embryos: Potential Role of the Aryl Hydrocarbon Receptor Toxicological Sciences : an Official Journal of the Society of Toxicology. May, 2013 | Pubmed ID: 23377616 Firemaster 550 (FM550) is an additive flame retardant formulation of brominated and aryl phosphate ester (APE) components introduced as a major replacement product for the commercial polybrominated diphenyl ether mixture (known as PentaBDE) used primarily in polyurethane foam. However, little is known about the potential effects of FM550-based ingredients during early vertebrate development. Therefore, we first screened the developmental toxicity of each FM550 component using zebrafish as an animal model. Based on these initial screening assays, we found that exposure to the brominated components as high as 10ÂµM resulted in no significant effects on embryonic survival or development, whereas exposure to triphenyl phosphate (TPP) or mono-substituted isopropylated triaryl phosphate (mono-ITP)-two APEs comprising almost 50% of FM550-resulted in targeted effects on cardiac looping and function during embryogenesis. As these cardiac abnormalities resembled aryl hydrocarbon receptor (AHR) agonist-induced phenotypes, we then exposed developing embryos to TPP or mono-ITP in the presence or absence of an AHR antagonist (CH223191) or AHR2-specific morpholino. Based on these studies, we found that CH223191 blocked heart malformations following exposure to mono-ITP but not TPP, whereas AHR2 knockdown failed to block the cardiotoxic effects of both components. Finally, using a cell-based human AHR reporter assay, we found that mono-ITP (but not TPP) exposure resulted in a significant increase in human AHR-driven luciferase activity at similar nominal concentrations as a potent reference AHR agonist (Î²-naphthoflavone). Overall, our findings suggest that two major APE components of FM550 induce severe cardiac abnormalities during early vertebrate development.

What Do Clinical Optometrists Like About Their Job? Clinical & Experimental Optometry : Journal of the Australian Optometrical Association. Feb, 2013 | Pubmed ID: 23379690 BACKGROUND: There are few publications describing what optometrists like about clinical work. The purpose of this paper is to explore what optometrists in practice find satisfying with their work and what they find stressful. METHODS: Sixty Australian optometrists participated in a 30-minute semi-structured telephone or face-to-face interview during the period August 2009 to March 2010. The interviews covered a range of topics related to ergonomics and physical comfort, including three questions related to satisfaction with clinical optometry, job satisfaction and self-perceived work-stress. These data were subject to qualitative and quantitative analysis. RESULTS: Participants reported that they liked clinical optometry because of work-related factors (for example, clinical challenge) (n = 47, 78 per cent), people-related factors (e.g. helping people) (n = 29, 48 per cent) and relationships with patients (n = 28, 47 per cent). Clinical freedom was the most frequently cited reason for participants liking their current job (n = 18, 30 per cent). Self-employed participants were more likely to value relationships with their patients (Chi-square, p < 0.01). Employee and locum participants were more likely to value relationships with staff (Chi-square, p < 0.05) and colleagues (Chi-square, p < 0.05). There were 32 participants (53 per cent) who perceived their work as stressful, most commonly related to clinical issues (n = 25, 42 per cent), workload demands (n = 20, 33 per cent) and management tasks (n = 15, 25 per cent). Clinical issues were a stressor for employee and locum participants (Chi-square, p < 0.01) and urban practitioners (Chi-square, p < 0.05). Management tasks were a stressor for independently practising participants (Chi-square, p < 0.01). CONCLUSION: Understanding what clinical optometrists like and find stressful about their work is important for employers, industry and the profession, as these are key elements of employment satisfaction. The information presented in this paper can be used as a basis for developing quantitative tools for assessing job satisfaction and job stress more extensively in the optometric profession.

Qualitative Exploration of Nurses' Decisions to Activate Rapid Response Teams Journal of Clinical Nursing. Feb, 2013 | Pubmed ID: 23388057 AIMS AND OBJECTIVES: To identify barriers and facilitators to nurses' decisions regarding activation of rapid response teams (RRTs) in hospitals. BACKGROUND: Hospitalised patients in the United States who experience cardiopulmonary arrest seldom recover. Most of these patients show signs of clinical deterioration prior to cardiopulmonary arrest. RRTs have been shown to decrease the incidence of cardiopulmonary arrest by bringing needed resources to unstable patients. Despite the evidence in support of the activation of RRTs, nurses do not always use this resource. Nurses' decisions to activate or not to activate the RRT are not clearly understood. DESIGN: We used a qualitative design for this study. METHODS: A purposive sample of 15 medical/surgical nurses was recruited from a small medical centre in the Midwest. Researchers used semistructured, open-ended questions to elicit subject responses regarding facilitators and barriers to activating RRTs. RESULTS: Themes emerged and were categorised as facilitators and barriers to calling the RRT. Facilitators and barriers were then subdivided into distinct subthemes: RRT characteristics and unit culture. The expertise of the RRT members and support and encouragement from nursing unit colleagues and leaders emerged as two potential facilitators. Communication of the RRT members and calling the physician first emerged as two potential barriers. We also identified educational factors that were not clearly facilitators or barriers to calling the RRT. CONCLUSIONS: Further study is needed using quantitative designs with larger sample sizes. RELEVANCE TO CLINICAL PRACTICE: Nurses can build upon knowledge of facilitators and barriers related to RRT characteristics and nursing unit culture.

Understanding the Stimulus of an Air-jet Aesthesiometer: Computerised Modelling and Subjective Interpretation Ophthalmic & Physiological Optics : the Journal of the British College of Ophthalmic Opticians (Optometrists). Mar, 2013 | Pubmed ID: 23406490 Assessment of corneal sensory function is more frequently being carried out using novel non-contact methods, which promise better stimulus control and a greater intensity range than more traditional techniques. An examination of the characteristics of the air-jet stimulus of these 'non-contact' aesthesiometers is important to enable an understanding of how these instruments stimulate the cornea. The purpose of this study was to model the air-jet stimulus of the CRCERT-Belmonte Aesthesiometer (CBA) and its interaction with the cornea.

Exposure to Flame Retardant Chemicals on Commercial Airplanes Environmental Health : a Global Access Science Source. 2013 | Pubmed ID: 23413926 Flame retardant chemicals are used in materials on airplanes to slow the propagation of fire. These chemicals migrate from their source products and can be found in the dust of airplanes, creating the potential for exposure.

Managing Compost Stability and Amendment to Soil to Enhance Soil Heating During Soil Solarization Waste Management (New York, N.Y.). May, 2013 | Pubmed ID: 23422041 Soil solarization is a method of soil heating used to eradicate plant pathogens and weeds that involves passive solar heating of moist soil mulched (covered) with clear plastic tarp. Various types of organic matter may be incorporated into soil prior to solarization to increase biocidal activity of the treatment process. Microbial activity associated with the decomposition of soil organic matter may increase temperatures during solarization, potentially enhancing solarization efficacy. However, the level of organic matter decomposition (stability) necessary for increasing soil temperature is not well characterized, nor is it known if various amendments render the soil phytotoxic to crops following solarization. Laboratory studies and a field trial were performed to determine heat generation in soil amended with compost during solarization. Respiration was measured in amended soil samples prior to and following solarization as a function of soil depth. Additionally, phytotoxicity was estimated through measurement of germination and early growth of lettuce seedlings in greenhouse assays. Amendment of soil with 10%(g/g) compost containing 16.9 mg CO2/gdry weight organic carbon resulted in soil temperatures that were 2-4 Â°C higher than soil alone. Approximately 85% of total organic carbon within the amended soil was exhausted during 22 days of solarization. There was no significant difference in residual respiration with soil depth down to 17.4 cm. Although freshly amended soil proved highly inhibitory to lettuce seed germination and seedling growth, phytotoxicity was not detected in solarized amended soil after 22 days of field solarization.

Zn(II) Stimulation of Fe(II)-activated Repression in the Iron-dependent Repressor from Mycobacterium Tuberculosis Biochemistry. Mar, 2013 | Pubmed ID: 23432191 Thermodynamic measurements of Fe(II) binding and activation of repressor function in the iron-dependent repressor from Mycobacterium tuberculosis (IdeR) are reported. IdeR, a member of the diphtheria toxin repressor family of proteins, regulates iron homeostasis and contributes to the virulence response in M. tuberculosis. Although iron is the physiological ligand, this is the first detailed analysis of iron binding and activation in this protein. The results showed that IdeR binds 2 equiv of Fe(II) with dissociation constants that differ by a factor of 25. The high- and low-affinity iron binding sites were assigned to physical binding sites I and II, respectively, using metal binding site mutants. IdeR was also found to contain a high-affinity Zn(II) binding site that was assigned to physical metal binding site II through the use of binding site mutants and metal competition assays. Fe(II) binding was modestly weaker in the presence of Zn(II), but the coupled metal binding-DNA binding affinity was significantly stronger, requiring 30-fold less Fe(II) to activate DNA binding compared to Fe(II) alone. Together, these results suggest that IdeR is a mixed-metal repressor, where Zn(II) acts as a structural metal and Fe(II) acts to trigger the physiologically relevant promoter binding. This new model for IdeR activation provides a better understanding of IdeR and the biology of iron homeostasis in M. tuberculosis.

Regulatory B Cell Frequency Correlates with Markers of HIV Disease Progression and Attenuates Anti-HIV CD8âº T Cell Function in Vitro Journal of Leukocyte Biology. May, 2013 | Pubmed ID: 23434518 HIV infection is associated with elevated expression of IL-10 and PD-L1, contributing to impairment of T cell effector functions. In autoimmunity, tumor immunology, and some viral infections, Bregs modulate T cell function via IL-10 production. In this study, we tested the hypothesis that during HIV infection, Bregs attenuate CD8(+) T cell effector function, contributing to immune dysfunction. We determined that in vitro, TLR2-, TLR9-, and CD40L-costimulated Bregs from HIV(-) individuals exhibited a high frequency of cells expressing IL-10 and PD-L1. Compared with Bregs from HIV(-) individuals, a significantly higher percentage of Bregs from HIV(+) individuals spontaneously expressed IL-10 (P=0.0218). After in vitro stimulation with HIV peptides, Breg-depleted PBMCs from HIV(+) individuals exhibited a heightened frequency of cytotoxic (CD107a(+); P=0.0171) and HIV-specific CD8(+) T cells compared with total PBMCs. Furthermore, Breg depletion led to enhanced proliferation of total CD8(+) and CD107a(+)CD8(+) T cells (P=0.0280, and P=0.0102, respectively). In addition, augmented CD8(+) T cell effector function in vitro was reflected in a 67% increased clearance of infected CD4(+) T cells. The observed Breg suppression of CD8(+) T cell proliferation was IL-10-dependent. In HIV(+) individuals, Breg frequency correlated positively with viral load (r=0.4324; P=0.0095), immune activation (r=0.5978; P=0.0005), and CD8(+) T cell exhaustion (CD8(+)PD-1(+); r=0.5893; P=0.0101). Finally, the frequency of PD-L1-expressing Bregs correlated positively with CD8(+)PD-1(+) T cells (r=0.4791; P=0.0443). Our data indicate that Bregs contribute to HIV-infection associated immune dysfunction by T cell impairment, via IL-10 and possibly PD-L1 expression.

Urinary Metabolites of Organophosphate Flame Retardants: Temporal Variability and Correlations with House Dust Concentrations Environmental Health Perspectives. May, 2013 | Pubmed ID: 23461877 A reduction in the use of polybrominated diphenyl ethers (PBDEs) because of human health concerns may result in an increased use of and human exposure to organophosphate flame retardants (OPFRs). Human exposure and health studies of OPFRs are lacking.

Concomitant Osteomyelitis and Avascular Necrosis of the Talus Treated with Talectomy and Tibiocalcaneal Arthrodesis Clinics in Podiatric Medicine and Surgery. Apr, 2013 | Pubmed ID: 23465813 The goal with Lisfranc fracture-dislocations is to regain joint congruity and reestablish midfoot stability to avoid debilitating posttraumatic arthrosis and chronic pain in the sensate patient. In the diabetic population, dense peripheral neuropathy and/or vascular disease are equally important and may alter the surgical approach to traumatic tarsometatarsal injuries. The initial diagnosis in the diabetic population may be delayed due to subtle radiographic findings and/or patient unawareness of trauma in the insensate foot. Failure to initiate treatment in the early stages of acute diabetic neuropathic Lisfranc injuries can predispose the patient to midfoot instability, potential ulceration, infection, and Charcot neuroarthropathy.

Diabetic Lisfranc Fracture-dislocations and Charcot Neuroarthropathy Clinics in Podiatric Medicine and Surgery. Apr, 2013 | Pubmed ID: 23465814 The goal with Lisfranc fracture-dislocations is to regain joint congruity and reestablish midfoot stability to avoid debilitating posttraumatic arthrosis and chronic pain in the sensate patient. In the diabetic population, dense peripheral neuropathy and/or vascular disease are equally important and may alter the surgical approach to traumatic tarsometatarsal injuries. The initial diagnosis in the diabetic population may be delayed due to subtle radiographic findings and/or patient unawareness of trauma in the insensate foot. Failure to initiate treatment in the early stages of acute diabetic neuropathic Lisfranc injuries can predispose the patient to midfoot instability, potential ulceration, infection, and Charcot neuroarthropathy.

Mechanism of [4Fe-4S](Cys)4 Cluster Nitrosylation is Conserved Among NO-responsive Regulators The Journal of Biological Chemistry. Apr, 2013 | Pubmed ID: 23471974 The Fumarate nitrate reduction (FNR) regulator from Escherichia coli controls expression of >300 genes in response to O2 through reaction with its [4Fe-4S] cluster cofactor. FNR is the master switch for the transition between anaerobic and aerobic respiration. In response to physiological concentrations of nitric oxide (NO), FNR also regulates genes, including the nitrate reductase (nar) operon, a major source of endogenous cellular NO, and hmp, which encodes an NO-detoxifying enzyme. Here we show that the [4Fe-4S] cluster of FNR reacts rapidly in a multiphasic reaction with eight NO molecules. Oxidation of cluster sulfide ions (S(2-)) to sulfane (S(0)) occurs, some of which remains associated with the protein as Cys persulfide. The nitrosylation products are similar to a pair of dinuclear dinitrosyl iron complexes, [Fe(I)2(NO)4(Cys)2](0), known as Roussin's red ester. A similar reactivity with NO was reported for the Wbl family of [4Fe-4S]-containing proteins found only in actinomycetes, such as Streptomyces and Mycobacteria. These results show that NO reacts via a common mechanism with [4Fe-4S] clusters in phylogenetically unrelated regulatory proteins that, although coordinated by four Cys residues, have different cluster environments. The reactivity of E. coli FNR toward NO, in addition to its sensitivity toward O2, is part of a hierarchal network that monitors, and responds to, NO, both endogenously generated and exogenously derived.

Whole-Body Heat Loss During Exercise in the Heat Is Not Impaired in Type 1 Diabetes Medicine and Science in Sports and Exercise. Mar, 2013 | Pubmed ID: 23475170 Purpose: To determine if individuals with type 1 diabetes exhibit impairments in local and whole-body heat loss responses that could impact core temperature regulation during exercise in the heat compared to matched, non-diabetic individuals. Methods: Twelve otherwise healthy individuals with type 1 diabetes (HbA1c = 7.7Â±0.3%) and 12 controls matched for age, sex, body surface area, and physical fitness cycled continuously for 60-min at a set rate of metabolic heat production (âˆ¼400W) in a whole-body direct calorimeter (35 Â°C and 20% relative humidity). Local sweat rate (ventilated capsule) was measured on the back and skin blood flow (SkBF, laser-Doppler velocimetry) on the forearm. Core (rectal and esophageal) and mean skin temperatures and heart rate were measured continuously. Whole-body heat exchange and change in body heat content were measured using simultaneous direct whole-body and indirect calorimetry. Results: The change (meanÂ±SE) in body heat content was similar between groups during exercise (Diabetes: 409Â±27; Control: 386Â±33 kJ, p=0.584) and recovery (Diabetes:-115Â±16; Control:-93Â±24 kJ, p=0.457). Local heat loss responses of sweating (p=0.783) and SkBF (p=0.078), as well as rectal temperature (Diabetes: 37.87Â±0.10; Control: 37.85Â±0.13 Â°C, p=0.977) and heart rate (Diabetes: 130Â±9 vs. Control: 127Â±7 beatsÂ·min, p=0.326) were comparable at the end of the exercise period. Conclusion: During light-to-moderate intensity exercise performed under conditions permitting full sweat evaporation, otherwise healthy type 1 diabetic individuals did not show impaired heat loss responses during heat exposure when compared to matched individuals without diabetes.

Comparison of the Effectiveness of Varenicline and Combination Nicotine Replacement Therapy for Smoking Cessation in Clinical Practice Mayo Clinic Proceedings. Mayo Clinic. Mar, 2013 | Pubmed ID: 23489449 To compare the effectiveness of varenicline and combination nicotine replacement therapy (NRT) for treating smokers attempting to stop, as it is unclear which of the 2 is more effective.

A Spinal Cord Window Chamber Model for in Vivo Longitudinal Multimodal Optical and Acoustic Imaging in a Murine Model PloS One. 2013 | Pubmed ID: 23516432 In vivo and direct imaging of the murine spinal cord and its vasculature using multimodal (optical and acoustic) imaging techniques could significantly advance preclinical studies of the spinal cord. Such intrinsically high resolution and complementary imaging technologies could provide a powerful means of quantitatively monitoring changes in anatomy, structure, physiology and function of the living cord over time after traumatic injury, onset of disease, or therapeutic intervention. However, longitudinal in vivo imaging of the intact spinal cord in rodent models has been challenging, requiring repeated surgeries to expose the cord for imaging or sacrifice of animals at various time points for ex vivo tissue analysis. To address these limitations, we have developed an implantable spinal cord window chamber (SCWC) device and procedures in mice for repeated multimodal intravital microscopic imaging of the cord and its vasculature in situ. We present methodology for using our SCWC to achieve spatially co-registered optical-acoustic imaging performed serially for up to four weeks, without damaging the cord or induction of locomotor deficits in implanted animals. To demonstrate the feasibility, we used the SCWC model to study the response of the normal spinal cord vasculature to ionizing radiation over time using white light and fluorescence microscopy combined with optical coherence tomography (OCT) in vivo. In vivo power Doppler ultrasound and photoacoustics were used to directly visualize the cord and vascular structures and to measure hemoglobin oxygen saturation through the complete spinal cord, respectively. The model was also used for intravital imaging of spinal micrometastases resulting from primary brain tumor using fluorescence and bioluminescence imaging. Our SCWC model overcomes previous in vivo imaging challenges, and our data provide evidence of the broader utility of hybridized optical-acoustic imaging methods for obtaining multiparametric and rich imaging data sets, including over extended periods, for preclinical in vivo spinal cord research.

The 3T3-L1 Adipocyte Glycogen Proteome Proteome Science. 2013 | Pubmed ID: 23521774 Glycogen is a branched polysaccharide of glucose residues, consisting of Î±-1-4 glycosidic linkages with Î±-1-6 branches that together form multi-layered particles ranging in size from 30 nm to 300 nm. Glycogen spatial conformation and intracellular organization are highly regulated processes. Glycogen particles interact with their metabolizing enzymes and are associated with a variety of proteins that intervene in its biology, controlling its structure, particle size and sub-cellular distribution. The function of glycogen in adipose tissue is not well understood but appears to have a pivotal role as a regulatory mechanism informing the cells on substrate availability for triacylglycerol synthesis. To provide new molecular insights into the role of adipocyte glycogen we analyzed the glycogen-associated proteome from differentiated 3T3-L1-adipocytes.

Predictors of Tris(1,3-dichloro-2-propyl) Phosphate Metabolite in the Urine of Office Workers Environment International. May, 2013 | Pubmed ID: 23523854 Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is a flame retardant widely used in furniture containing polyurethane foam. It is a carcinogen, endocrine disruptor, and potentially neurotoxic. Our objectives were to characterize exposure of adult office workers (n=29) to TDCPP by measuring its primary metabolite, bis(1,3-dichloro-2-propyl) phosphate (BDCPP), in their urine; measuring TDCPP in dust from their homes; offices and vehicles; and assessing possible predictors of exposure. We identified TDCPP in 99% of dust (GM=4.43Î¼g/g) and BDCPP in 100% of urine samples (GM=408pg/mL). Concentrations of TDCPP were significantly higher in dust from vehicles (GM=12.5Î¼g/g) and offices (GM=6.06Î¼g/g) than in dust from the main living area (GM=4.21Î¼g/g) or bedrooms (GM=1.40Î¼g/g) of worker homes. Urinary BDCPP concentrations among participants who worked in a new office building were 26% of those who worked in older buildings (p=0.01). We found some evidence of a positive trend between urinary BDCPP and TDCPP in office dust that was not observed in the other microenvironments and may be related to the timing of urine sample collection during the afternoon of a workday. Overall our findings suggest that exposure to TDCPP in the work environment is one of the contributors to the personal exposure for office workers. Further research is needed to confirm specific exposure sources (e.g., polyurethane foam), determine the importance of exposure in other microenvironments such as homes and vehicles, and address the inhalation and dermal exposure pathways.

Do Heat Events Pose a Greater Health Risk for Individuals with Type 2 Diabetes? Diabetes Technology & Therapeutics. Jun, 2013 | Pubmed ID: 23530578 Chronic medical conditions such as type 2 diabetes may alter the body's normal response to heat. Evidence suggests that the local heat loss response of skin blood flow (SkBF) is affected by diabetes-related impairments in both endothelium-dependent and non-endothelium-dependent mechanisms, resulting in lower elevations in SkBF in response to a heat or pharmacological stimulus. Thermoregulatory sweating may also be diminished by type 2 diabetes, impairing the body's ability to transfer heat from its core to the environment. Diabetes-associated co-morbidities and the medications (particularly those affecting fluid balance) required to treat these conditions may exacerbate the risk of heat-related illness by decreasing SkBF and sweating further. Unfortunately, the majority of studies measure local heat loss responses in the hands and feet and lack measures of core temperature. Therefore, the impact of these impairments on whole-body heat loss remains unknown. This review addresses heat-related vulnerability in individuals with type 2 diabetes by examining the literature related to heat loss responses in this population. Type 2 diabetes, its associated co-morbidities, and the medications required in their treatment may cause dehydration, lower SkBF, and reduced sweating, which could consequently impair thermoregulation. This effect is most evident in individuals with poor blood glucose control. Although type 2 diabetes can be associated with impairments in SkBF and sweating, more physically active individuals requiring fewer medications and having good blood glucose control may be able to tolerate heat as well as those of similar age and body composition.

Using Whole Mount in Situ Hybridization to Examine Thyroid Hormone Deiodinase Expression in Embryonic and Larval Zebrafish: a Tool for Examining OH-BDE Toxicity to Early Life Stages Aquatic Toxicology (Amsterdam, Netherlands). May, 2013 | Pubmed ID: 23531416 Polybrominated diphenyl ethers (PBDEs) and their oxidative metabolites (hydroxylated PBDEs; OH-BDEs) are known endocrine disrupting contaminants that have been shown to disrupt thyroid hormone regulation both in mammals and in fish. The purpose of this study was to determine the precise organ and tissue locations that express genes critical to thyroid hormone regulation in developing zebrafish (Danio rerio), and to determine the effects of an OH-BDE on their expression. While RT-PCR can provide quantitative data on gene expression, it lacks spatial sensitivity to examine localized gene expression; and, isolation of organs from zebrafish embryos is technically difficult, if not impossible. For this reason, the present study used whole mount in situ hybridization to simultaneously localize and quantify gene expression in vivo. While PBDEs and OH-BDEs have been shown to inhibit the activity and expression of deiodionases, a family of enzymes that regulate thyroid hormone concentrations intracellularly, it is unclear whether or not they can affect regional expression of the different isoforms during early development. In this study we investigated deiodinase 1 (Dio1), deiodinase 2 (Dio2), and deiodinase 3 (Dio3) mRNA expression at the following life stages (2, 8, and 1k-cells; 50%-epiboly, 6 and 18-somites, 22, 24, 48, 72 hpf and/or 10 dpf) in zebrafish and found life stage specific expression of these genes that were highly localized. To demonstrate the use of this technique for investigating potential endocrine disrupting effects, zebrafish embryos were exposed to 1, 10 and 100nM 6-OH-BDE-47. Significant increases in mean intensity of Dio1 and Dio3 expression in the periventricular zone of brain and pronephric duct, respectively (quantified by measuring intensity of coloration using ImageJ analysis software) were observed, suggesting localized response at the HPT axis with the possibility of impacting neurodevelopment. Our results demonstrate effects of OH-BDEs on thyroid regulating gene expression and provide more insight into potential sites of injury during early life stages.

Older Adults with Type 2 Diabetes Store More Heat During Exercise Medicine and Science in Sports and Exercise. Mar, 2013 | Pubmed ID: 23542894 It is unknown if diabetes-related reductions in local skin blood flow (SkBF) and sweating (LSR) measured during passive heat stress translate into greater heat storage during exercise in the heat in individuals with type 2 diabetes (T2D) compared to non-diabetic control (CON) subjects. PURPOSE: To examine the effects of T2D on whole-body heat exchange during exercise in the heat. METHODS: Ten (6 males and 4 females) adults with T2D and 10 adults (6 males and 4 females) without diabetes matched for age, sex, body surface area, and fitness cycled continuously for 60 min at a fixed rate of metabolic heat production (âˆ¼370 W) in a whole-body direct calorimeter (30Â°C and 20% RH). Upper back LSR, forearm SkBF and rectal temperature (Tre) and heart rate were measured continuously. Whole-body heat loss and changes in body heat content (Î”Hb) were determined using simultaneous direct whole-body and indirect calorimetry. RESULTS: Whole-body heat loss was significantly attenuated from 15 min throughout the remaining exercise with the differences becoming more pronounced over time for T2D relative to CON (p=0.004). This resulted in a significantly greater Î”Hb in T2D (360Â±33; CON: 265Â±28 kJ, p=0.013). No differences were measured during recovery (T2D: -87Â±22; CON: -132Â±21 kJ, p=0.076). By the end of the 60-min recovery, the T2D group lost only 21% (79 kJ) of the total heat gained during exercise whereas their non-diabetic counterparts lost in excess of 55% (131 kJ). No differences were observed in LSR (p=0.361), SkBF (p=0.528), Tre (p=0.388) or heart rate (p=0.179) during exercise or recovery. CONCLUSION: Older adults with T2D have a reduced capacity to dissipate heat during exercise resulting a greater heat storage and therefore level of thermal strain.

Human Exposure Assessment of Indoor Dust: Webster and Stapleton Respond Environmental Health Perspectives. Apr, 2013 | Pubmed ID: 23548261

Investigating a Novel Flame Retardant Known As V6: Measurements in Baby Products, House Dust, and Car Dust Environmental Science & Technology. May, 2013 | Pubmed ID: 23565680 With the phase-out of polybrominated diphenyl ether (PBDE) flame retardants, the use of new and alternate flame retardants has been increasing. 2,2-bis(chloromethyl)propane-1,3-diyltetrakis(2-chloroethyl) bisphosphate, known as V6, is a flame retardant applied to polyurethane foam commonly found in furniture and automobile foam. However, to the authors' knowledge, no research has been conducted on V6 levels in the environment. The intention of this study was to measure the concentration of V6 in foam collected from baby products where it was recently detected and measure levels in dust samples collected from homes and automobiles in the Boston, MA area. To accomplish this, a pure V6 commercial standard was purchased from a Chinese manufacturer and purified (>98%). An analytical method to measure V6 in dust samples using liquid chromatography tandem mass spectrometry (LC/MS-MS) was developed. Extraction was conducted using accelerated solvent extraction (ASE) and extracts were purified using an ENVI-Florisil SPE column (500 mg, 3 mL). V6 was measured in foam samples collected from baby products with a concentration ranging from 24,500,000 to 59,500,000 ng/g of foam (n = 12, average Â± sd: 46,500,000 Â± 12,000,000 ng/g; i.e., on average, 4.6% of the foam mass was V6). V6 was also detected in 19 of 20 car dust samples and 14 of 20 house dust samples analyzed. The concentration of V6 in the house dust ranged from

Biomimetic Model to Reconstitute Angiogenic Sprouting Morphogenesis in Vitro Proceedings of the National Academy of Sciences of the United States of America. Apr, 2013 | Pubmed ID: 23569284 Angiogenesis is a complex morphogenetic process whereby endothelial cells from existing vessels invade as multicellular sprouts to form new vessels. Here, we have engineered a unique organotypic model of angiogenic sprouting and neovessel formation that originates from preformed artificial vessels fully encapsulated within a 3D extracellular matrix. Using this model, we screened the effects of angiogenic factors and identified two distinct cocktails that promoted robust multicellular endothelial sprouting. The angiogenic sprouts in our system exhibited hallmark structural features of in vivo angiogenesis, including directed invasion of leading cells that developed filopodia-like protrusions characteristic of tip cells, following stalk cells exhibiting apical-basal polarity, and lumens and branches connecting back to the parent vessels. Ultimately, sprouts bridged between preformed channels and formed perfusable neovessels. Using this model, we investigated the effects of angiogenic inhibitors on sprouting morphogenesis. Interestingly, the ability of VEGF receptor 2 inhibition to antagonize filopodia formation in tip cells was context-dependent, suggesting a mechanism by which vessels might be able to toggle between VEGF-dependent and VEGF-independent modes of angiogenesis. Like VEGF, sphingosine-1-phosphate also seemed to exert its proangiogenic effects by stimulating directional filopodial extension, whereas matrix metalloproteinase inhibitors prevented sprout extension but had no impact on filopodial formation. Together, these results demonstrate an in vitro 3D biomimetic model that reconstitutes the morphogenetic steps of angiogenic sprouting and highlight the potential utility of the model to elucidate the molecular mechanisms that coordinate the complex series of events involved in neovascularization.

Tear Lipid Layer and Contact Lens Comfort: a Review Eye & Contact Lens. May, 2013 | Pubmed ID: 23584045 This review describes the impact of contact lens wear on the tear film lipid layer and how changes in the lipid layer might modulate contact lens-related discomfort. Relevant clinical, functional, and biochemical aspects of the tear film lipid layer are reviewed. Contact lens wear modulates these aspects of the lipid layer, specifically the prelens lipid layer thickness is reduced; tear evaporation rate is increased; tear breakup time is reduced; and the concentration of lipid components such as cholesterol esters, wax esters, and phospholipids varies. The full implications of these changes are unclear; however, there is some evidence that contact lens-related discomfort is associated with a thinner prelens lipid layer, increased lipid degradation, and greater secretory phospholipase A2 activity. Certain fatty acids appear to be associated with maintaining the structural stability of the tear film but their role in retarding tear evaporation and modulating contact lens-related discomfort remains to be elucidated.

Bayesian Analysis and Classification of Two Enzyme-linked Immunosorbent Assay Tests Without a Gold Standard Statistics in Medicine. Apr, 2013 | Pubmed ID: 23592433 Reconciling two quantitative enzyme-linked immunosorbent assay tests for an antibody to an RNA virus, in a situation without a gold standard and where false negatives may occur, is the motivation for this work. False negatives occur when access of the antibody to the binding site is blocked. On the basis of the mechanism of the assay, a mixture of four bivariate normal distributions is proposed with the mixture probabilities depending on a two-stage latent variable model including the prevalence of the antibody in the population and the probabilities of blocking on each test. There is prior information on the prevalence of the antibody, and also on the probability of false negatives, and so a Bayesian analysis is used. The dependence between the two tests is modeled to be consistent with the biological mechanism. Bayesian decision theory is utilized for classification.The proposed method is applied to the motivating data set to classify the data into two groups: those with and those without the antibody. Simulation studies describe the properties of the estimation and the classification. Sensitivity to the choice of the prior distribution is also addressed by simulation. The same model with two levels of latent variables is applicable in other testing procedures such as quantitative polymerase chain reaction tests, where false negatives occur when there is a mutation in the primer sequence. Copyright Â© 2013 John Wiley & Sons, Ltd.

Parenteral Fish Oil Lipid Emulsions in the Critically Ill: A Systematic Review and Meta-Analysis JPEN. Journal of Parenteral and Enteral Nutrition. Apr, 2013 | Pubmed ID: 23609773 Introduction: Ï‰-3 Polyunsaturated fatty acids contained in fish oils (FO) possess major anti-inflammatory, antioxidant, and immunologic properties that could be beneficial during critical illness. We hypothesized that parenteral FO-containing emulsions may improve clinical outcomes in the critically ill. Methods: We searched computerized databases from 1980-2012. We included randomized controlled trials (RCTs) conducted in critically ill adult patients that evaluated FO-containing emulsions, either in the context of parenteral nutrition (PN) or enteral nutrition (EN). Results: A total of 6 RCTs (n = 390 patients) were included; the mean methodological score of all trials was 10 (range, 6-13). When the results of these studies were aggregated, FO-containing emulsions were associated with a trend toward a reduction in mortality (risk ratio [RR], 0.71; 95% confidence interval [CI], 0.49-1.04; P = .08; heterogeneity I(2) = 0%) and a reduction in the duration of mechanical ventilation (weighted mean difference in days [WMD], -1.41; 95% CI, -3.43 to 0.61; P = .17). However, this strategy had no effect on infections (RR, 0.76; 95% CI, 0.42-1.36; P = .35) and intensive care unit length of stay (WMD, -0.46; 95% CI, -4.87 to 3.95; P = .84, heterogeneity I(2) = 75%). Conclusion: FO-containing lipid emulsions may be able to decrease mortality and ventilation days in the critically ill. However, because of the paucity of clinical data, there is inadequate evidence to recommend the routine use of parenteral FO. Large, rigorously designed RCTs are required to elucidate the efficacy of parenteral FO in the critically ill.

Qualitative Analysis of Cocaine and Heroin Users' Main Partner Sex-risk Behavior: is Safety in Love Safety in Health? Addiction Science & Clinical Practice. 2013 | Pubmed ID: 23618318 In 2009, 27% of the 48,100 estimated new cases of HIV were attributed to heterosexual contact with an infected or at-risk person. Sexually active adults are less likely to use condoms in relationships with main partners than with non-regular partners, despite general knowledge that condom use reduces HIV transmission.

Dabigatran, Intracranial Hemorrhage, and the Neurosurgeon Neurosurgical Focus. May, 2013 | Pubmed ID: 23634926 Dabigatran etexilate (Pradaxa) is a novel oral anticoagulant that has gained FDA approval for the prevention of ischemic stroke and systemic embolism in patients with nonvalvular atrial fibrillation. In randomized trials, the incidence of hemorrhagic events has been demonstrated to be lower in patients treated with dabigatran compared with the traditional anticoagulant warfarin. However, dabigatran does not have reliable laboratory tests to measure levels of anticoagulation and there is no pharmacological antidote. These drawbacks are challenging in the setting of intracerebral hemorrhage. In this article, the authors provide background information on dabigatran, review the existing anecdotal experiences with treating intracerebral hemorrhage related to dabigatran therapy, present a case study of intracranial hemorrhage in a patient being treated with dabigatran, and suggest clinical management strategies. The development of reversal agents is urgently needed given the growing number of patients treated with this medication.

Impact on Caesarean Section Rates Following Injections of Sterile Water (ICARIS): a Multicentre Randomised Controlled Trial BMC Pregnancy and Childbirth. 2013 | Pubmed ID: 23642147 Sterile water injections have been used as an effective intervention for the management of back pain during labour. The objective of the current research is to determine if sterile water injections, as an intervention for back pain in labour, will reduce the intrapartum caesarean section rate.

Maternal Engineered Nanomaterial Exposure and Fetal Microvascular Function: Does the Barker Hypothesis Apply? American Journal of Obstetrics and Gynecology. Apr, 2013 | Pubmed ID: 23643573 OBJECTIVE: The continued development and use of engineered nanomaterials (ENM) has given rise to concerns over the potential for human health effects. While the understanding of cardiovascular ENM toxicity is improving, one of the most complex and acutely demanding "special" circulations is the enhanced maternal system to support fetal development. The "Barker Hypothesis" proposes that fetal development within a hostile gestational environment may predispose/program future sensitivity. Therefore, the objective of this study was two-fold: 1) to determine if maternal ENM exposure alters uterine and/or fetal microvascular function and 2) test the Barker Hypothesis at the microvascular level. STUDY DESIGN: Pregnant (gestation day 10) Sprague-Dawley rats were exposed to nano-titanium dioxide aerosols (11.3Â±0.039 (mg/m(3))/hour, 5 hours/day, 8.2Â±0.85 days) to evaluate the maternal and fetal microvascular consequences of maternal exposure. Microvascular tissue isolation (gestation day 20) and arteriolar reactivity studies (

Pulmonary Cerium Dioxide Nanoparticle Exposure Differentially Impairs Coronary and Mesenteric Arteriolar Reactivity Cardiovascular Toxicology. May, 2013 | Pubmed ID: 23645470 Cerium dioxide nanoparticles (CeO2 NPs) are an engineered nanomaterial (ENM) that possesses unique catalytic, oxidative, and reductive properties. Currently, CeO2 NPs are being used as a fuel catalyst but these properties are also utilized in the development of potential drug treatments for radiation and stroke protection. These uses of CeO2 NPs present a risk for human exposure; however, to date, no studies have investigated the effects of CeO2 NPs on the microcirculation following pulmonary exposure. Previous studies in our laboratory with other nanomaterials have shown impairments in normal microvascular function after pulmonary exposures. Therefore, we predicted that CeO2 NP exposure would cause microvascular dysfunction that is dependent on the tissue bed and dose. Twenty-four-hour post-exposure to CeO2 NPs (0-400Â Î¼g), mesenteric, and coronary arterioles was isolated and microvascular function was assessed. Our results provided evidence that pulmonary CeO2 NP exposure impairs endothelium-dependent and endothelium-independent arteriolar dilation in a dose-dependent manner. The CeO2 NP exposure dose which causes a 50Â % impairment in arteriolar function (EC50) was calculated and ranged from 15 to 100Â Î¼g depending on the chemical agonist and microvascular bed. Microvascular assessments with acetylcholine revealed a 33-75Â % reduction in function following exposure. Additionally, there was a greater sensitivity to CeO2 NP exposure in the mesenteric microvasculature due to the 40Â % decrease in the calculated EC50 compared to the coronary microvasculature EC50. CeO2 NP exposure increased mean arterial pressure in some groups. Taken together, these observed microvascular changes may likely have detrimental effects on local blood flow regulation and contribute to cardiovascular dysfunction associated with particle exposure.

Development and Validation of the 21-item Children's Vision for Living Scale (CVLS) by Rasch Analysis Clinical & Experimental Optometry : Journal of the Australian Optometrical Association. May, 2013 | Pubmed ID: 23646873 BACKGROUND: The aim was to develop and validate an instrument called the 'Children's Vision for Living Scale' (CVLS) for the assessment of vision-related quality of life in Saudi Arabian children with and without amblyopia. METHODS: A 43-item child self-report questionnaire was initially developed based on interviews with children with amblyopia, their parents and eye-care professionals, and a literature review. Following a process that involved the removal of redundant items, 28 items remained and were piloted on children aged five to 12 years with and without amblyopia (n = 48 amblyopic, n = 53 non-amblyopic) living in Saudi Arabia. Rasch analysis was applied to determine whether the 28-item questionnaire fitted the Rasch model. Rasch analysis was used to assess the validity and reliability of the questionnaire. Principal components analysis (PCA) was used to check dimensionality. A 21-item questionnaire resulting from this process was administered in children with (n = 81) and without (n = 82) amblyopia in Saudi Arabia for further validation. RESULTS: The final 21-item questionnaire had good validity and reliability as demonstrated by person separation of 2.02, person reliability of 0.80 (mean square and standard deviation: infit = 1.01 Â± 0.39; outfit = 1.01 Â± 0.40) and item reliability of 0.93 (item infit range = 1.33 to 0.78; item outfit range = 0.78 to 1.30). The mean difference between person and item scores of 0.33 Â± 0.53 logits (scale range, 2 to -2) indicates that the items are well targeted to the populations. The PCA (dimensionality measures) shows the percentage of variance explained by measures equal to 26.4 per cent (modelled 26.9 per cent) and an eigenvalue of the first contrast of 2.5, which demonstrated good stability. CONCLUSION: The 21-item CVLS is a valid uni-dimensional child self-report instrument for the assessment of the impact of amblyopia on vision-related quality of life in children with and without amblyopia living in Saudi Arabia.

How Does Rate of Smoking Cessation Vary by Age, Gender and Social Grade? Findings from a Population Survey in England Addiction (Abingdon, England). May, 2013 | Pubmed ID: 23668684 AIMS: To assess the incidence of long-term smoking cessation as a function of age, gender, social grade and their interactions. DESIGN AND SETTING: Cross-sectional surveys of population representative samples of smokers in England. PARTICIPANTS: A total of 24â€‰094 ever smokers (â‰¥21 and â‰¤60 years of age) participating in household surveys between November 2006 and February 2011. MEASUREMENTS: The ratio of long-term (>1 year) ex-smokers to ever-smokers was calculated for each age. Regression analyses were used to model the association between age and quit ratio, with the change in quit ratio by year of age n years versus all years up to n-1 years, yielding an estimate of the quitting incidence at that age. Analyses were conducted for the entire sample and then for the sample stratified by gender and social grade, and interactions assessed between these variables. FINDINGS: A cubic trend was needed to fit the data. The estimated quitting incidence between ages 21 and 30 was 1.5% (95% CI: 1.0%-2.0%), between 31 and 50 it was 0.3% (95% CI: 0.2%-0.5%) and between 51 and 60 it was 1.2% (95% CI: 0.7%-1.7%). Age interacted with gender and social grade: women and smokers from higher social grades had a higher incidence of quitting than men and those from lower social grades specifically in young adulthood. CONCLUSIONSâ€ƒ: The incidence of smoking cessation in England appears to be greater in young and old adults compared with those in middle age. Women and higher social grade smokers show a greater incidence of quitting than men and those from lower social grades specifically in young adulthood.

The American Suntanning Association: a "science-first Organization" with a Biased Scientific Agenda JAMA Dermatology (Chicago, Ill.). May, 2013 | Pubmed ID: 23677074

Saving the Patient with Post-ACS Cardiogenic Shock Minerva Cardioangiologica. Jun, 2013 | Pubmed ID: 23681131 The adoption of early revascularization as the preferred strategy in all ST-elevation myocardial infarctions (STEMI) and high risk acute coronary syndromes (ACS) without ST elevation resulted in a considerable reduction in the incidence of post-ACS cardiogenic shock (CS) however the incidence of CS on hospital arrival has not changed. In-hospital and 30 day mortality from CS remains excessively high in facilities with coronary revascularization capabilities. Trials investigating the incremental value of either intra-aortic counter-pulsation (IACP) or advanced MCS did not demonstrate a meaningful mortality reduction. Mortality remains 45-60% and depends on clinical characteristics of the patient, timely and successful revascularization and advanced MCS in suitable candidates. Most CS survivors demonstrate satisfactory functional capacity and quality of life. The authors propose the "Guthrie classification" for post-ACS CS. This classification promotes better characterization of CS patients enrolled in clinical trials and registries. It also allows the clinician to better define the goals and benefits of therapy for the CS subjects. The precise pathophysiology of post-ACS CS remains poorly understood at the biochemical and cellular level. Uncovering and modifying these processes remains key to any fundamental change in post-ACS CS outcomes.

Injury Trends and Mortality in Adult Patients with Major Trauma in New South Wales The Medical Journal of Australia. May, 2013 | Pubmed ID: 23682886

A Preliminary Identification and Determination of Characteristic Volatile Organic Compounds from Cotton, Polyester and Terry-towel by Headspace Solid Phase Microextraction Gas Chromatography-mass Spectrometry Journal of Chromatography. A. Jun, 2013 | Pubmed ID: 23683894 Analysis of fifteen volatile organic compounds previously associated with laundry malodour has been investigated using headspace solid phase microextraction gas chromatography-mass spectrometry. Limits of detection (all determined on a 25 cm(2) area of fabric) ranged from a low of 0.4 ng (for guaiacol) through to a high of 28 ng (for 3-methylindole) on cotton; values on polyester ranged from a low of 0.7 ng (for dimethyl trisulfide) through to a high of 37 ng (for 3-methylindole); and, values on terry-towel ranged from a low of 1.7 ng (for guaiacol) through to a high of 157 ng (for ethyl benzene). There was a lack of correlation between the level of malodour and the occurrence of any of the VOCs detected; it could be that other compounds not evaluated in this study are responsible for malodour or it could be a collaborative effect of the various compounds studied.

Quantitative and Simultaneous Translational Control of Distinct Mammalian MRNAs Nucleic Acids Research. Jul, 2013 | Pubmed ID: 23685611 The introduction of multiple genes into cells is increasingly required for understanding and engineering biological systems. Small-molecule-responsive transcriptional regulation has been widely used to control transgene expression. In contrast, methods for specific and simultaneous regulation of multiple genes with a single regulatory protein remain undeveloped. In this report, we describe a method for quantitatively tuning the expression of multiple transgenes with a translational regulatory protein. A protein that binds a specific RNA motif inserted in the 5'-untranslated region (UTR) of an mRNA modulates the translation of that message in mammalian cells. We provide two independent mechanisms by which to rationally fine-tune the output: the efficiency of translation correlates well with the distance between the inserted motif and the 5' terminus of the mRNA and is further modulated by the tandem insertion of multiple RNA motifs. The combination of these two approaches allowed us to fine-tune the translational efficiency of target mRNAs over a wide dynamic range. Moreover, we controlled the expression of two transgenes simultaneously and specifically by engineering each cis-regulatory 5'-UTR. The approach provides a useful alternative regulatory layer for controlling gene expression in biological research and engineering.

Does Thyroid Disruption Contribute to the Developmental Neurotoxicity of Chlorpyrifos? Environmental Toxicology and Pharmacology. Apr, 2013 | Pubmed ID: 23686008 Although organophosphate pesticides are not usually characterized as "endocrine disruptors," recent work points to potential, long-term reductions of circulating thyroid hormones after developmental exposures to chlorpyrifos that are devoid of observable toxicity. We administered chlorpyrifos to developing rats on gestational days 17-20 or postnatal days 1-4, regimens that produce distinctly different, sex-selective effects on neurobehavioral performance. The prenatal regimen produced a small, but statistically significant reduction in brain thyroxine levels from juvenile stages through adulthood; in contrast, postnatal exposure produced a transient elevation in young adulthood. However, in neither case did we observe the sex-selectivity noted earlier for neurobehavioral outcomes of these specific treatment regimens, or as reported earlier for effects on serum T4 in developing mice. Thus, although chlorpyrifos has the potential to disrupt thyroid status sufficiently to alter brain thyroid hormone levels, the effect is small, and any potential contribution to neurobehavioral abnormalities remains to be proven.

GB Virus C Particles Inhibit T Cell Activation Via Envelope E2 Protein-Mediated Inhibition of TCR Signaling Journal of Immunology (Baltimore, Md. : 1950). Jun, 2013 | Pubmed ID: 23686495 Viruses enter into complex interactions within human hosts, leading to facilitation or suppression of each other's replication. Upon coinfection, GB virus C (GBV-C) suppresses HIV-1 replication in vivo and in vitro, and GBV-C coinfection is associated with prolonged survival in HIV-infected people. GBV-C is a lymphotropic virus capable of persistent infection. GBV-C infection is associated with reduced T cell activation in HIV-infected humans, and immune activation is a critical component of HIV disease pathogenesis. We demonstrate that serum GBV-C particles inhibited activation of primary human T cells. T cell activation inhibition was mediated by the envelope glycoprotein E2, because expression of E2 inhibited TCR-mediated activation of Lck. The region on the E2 protein was characterized and revealed a highly conserved peptide motif sufficient to inhibit TCR-mediated signaling. The E2 region contained a predicted Lck substrate site, and substitution of an alanine or histidine for the tyrosine reversed TCR-signaling inhibition. GBV-C E2 protein and a synthetic peptide representing the inhibitory amino acid sequence were phosphorylated by Lck in vitro. The synthetic peptide also inhibited TCR-mediated activation of primary human CD4(+) and CD8(+) T cells. Extracellular microvesicles from GBV-C E2-expressing cells contained E2 protein and inhibited TCR signaling in bystander T cells not expressing E2. Thus, GBV-C reduced global T cell activation via competition between its envelope protein E2 and Lck following TCR engagement. This novel inhibitory mechanism of T cell activation may provide new approaches for HIV and immunoactivation therapy.

Equity in Public Health: An Epigenetic Perspective Public Health Genomics. May, 2013 | Pubmed ID: 23689619 Evidence emerging from the study of epigenetics and epigenomics challenges notions of health by enhancing understanding of disease etiologies and improving awareness of new health risks. New paradigms arising from epigenetic and epigenomic research present challenging cases through which to debate theories of justice in health because they expand the concept of health and, controversially, place value on what was previously assumed to be 'healthy' individual variance. Discoveries of the dynamic nature of the epigenome and its variable sensitivity towards change in numerous phenomena add further complexity to the assessment of health inequalities. Such evidence can cast doubt on perceptions of justice in health, which in turn raises questions over the suitability of actions taken in pursuit of equity. This article discusses how recent developments in epigenetics and epigenomics may impact upon assessments of equity in health. A review of literature discussing possible health risks associated with acquired yet heritable epigenetic variance is used to highlight the diversity of possible pathways through which health may be influenced. From this context, the consideration of health risk with respect to epigenetics, it is argued, demands a more inclusive concept of health when used in discussions of inequities.

Maternal Overweight and Obesity: a Survey of Clinicians' Characteristics and Attitudes, and Their Responses to Their Pregnant Clients BMC Pregnancy and Childbirth. 2013 | Pubmed ID: 23692981 Statewide (Queensland) Clinical Guidelines reflecting current best practice have recently become available for the management of pregnancy-related obesity. Our aim was to assess staff knowledge about, adherence to, and characteristics that influence delivery of care according to these Guidelines.

Personal Consequences of Work-related Physical Discomfort: an Exploratory Study Clinical & Experimental Optometry : Journal of the Australian Optometrical Association. May, 2013 | Pubmed ID: 23701021 BACKGROUND: Work-related physical discomfort has been reported in Australian optometrists. The purpose of this paper is to explore the personal consequences of work-related discomfort. METHODS: Forty-seven optometrists with self-reported work-related discomfort participated in a 30-minute telephone or face-to-face interview related to ergonomics and physical comfort. Self-employed, employee, locum and retired optometrists participated. Four avenues were investigated; namely, description of discomfort, non-work contributing factors, whether the participant has ever stopped work due to discomfort, and the treatments accessed to alleviate discomfort. These data were subject to qualitative and quantitative analyses. RESULTS: Reported discomfort ranged from mild to severe. Eight participants (17 per cent) ascribed their discomfort entirely to work and seven (15 per cent) cited non-work factors as the cause. Many participants (32, 68 per cent) reported that non-work factors, for example, sport and driving, aggravated existing work-related discomfort and for some, their discomfort impacted on home and leisure activities. There were 15 participants (32 per cent), who have stopped work because of discomfort, including two who have ceased working as an optometrist and two who now work reduced hours. The majority (32) continue to work despite discomfort. Many participants (31, 66 per cent) seek treatment to alleviate discomfort, with seven participants (15 per cent) reporting that they receive multiple therapies per week. Work-related discomfort was generally viewed as a personal issue, with most participants accessing treatment in their own time (27, 57 per cent) and funding it personally or with private health insurance. Only four participants have received funding through workers' compensation or income protection insurance. CONCLUSIONS: Work-related discomfort has significant financial and personal costs for some Australian optometrists. These qualitative data can be used to develop quantitative tools for assessing the impact of discomfort on quality of life for optometrists and their families. The results also highlight the need for preventative action to reduce work-related discomfort within the optometric profession.

The Type 1 Pili Regulator Gene FimX and Pathogenicity Island PAI-X As Molecular Markers of Uropathogenic Escherichia Coli Microbiology (Reading, England). Jun, 2013 | Pubmed ID: 23744903 Uropathogenic Escherichia coli (UPEC) fall within a larger group of isolates producing extraintestinal disease. UPEC express type 1 pili as a critical virulence determinant mediating adherence to and invasion into urinary tract tissues. Type 1 pili expression is under regulation by a family of site-specific recombinases, including FimX, which is encoded from a genomic islet called PAI-X for Pathogenicity Islet of FimX. Using a new multiplex PCR, fimX and the additional PAI-X genes were found to be highly associated with UPEC (144/173 = 83.2%), and more prevalent in UPEC of lower urinary tract origin (105/120 = 87.5%) than upper urinary tract origin (39/53 = 74%; p-value < 0.05) or commensal isolates (28/78 = 36%; p-value â‰¤ 0.0001). The Fim-like recombinase gene fimX is the only family member that has a significant association with UPEC compared to commensal isolates. Our results indicate PAI-X genes, including the type 1 pili regulator gene fimX, are highly prevalent among UPEC isolates and have a strong positive correlation with genomic virulence factors, suggesting a potential role for PAI-X in the ExPEC lifestyle.

Linguistic Acculturation and Skin Cancer-related Behaviors Among Hispanics in the Southern and Western United States JAMA Dermatology (Chicago, Ill.). Jun, 2013 | Pubmed ID: 23752366 OBJECTIVE To examine the association between linguistic acculturation (assessed using the Language Use and Linguistic Preference subscales from the Bidimensional Acculturation Scale for Hispanics) and skin cancer-related behaviors among US Hispanic adults to determine whether, compared with Hispanics denoted as Spanish-acculturated, English-acculturated Hispanics would report less frequent shade seeking and use of sun protective clothing and higher rates of sunscreen use, sunbathing, and indoor tanning. DESIGN Online survey study conducted in September 2011. SETTING Five southern and western US states. PARTICIPANTS A population-based sample of 788 Hispanic adults drawn from a nationally representative web panel. MAIN OUTCOME MEASURES Self-reported sunscreen use, shade seeking, use of sun protective clothing, sunbathing, and indoor tanning. RESULTS Multivariate regression analyses were conducted to examine predictors of the skin cancer-related behaviors. As hypothesized, English-acculturated Hispanics had lower rates of shade seeking and use of sun protective clothing and reported higher rates of sunbathing and indoor tanning than Spanish-acculturated Hispanics. English-acculturated Hispanics and bicultural Hispanics (ie, those with high Spanish and high English acculturation) reported comparably high rates of sunbathing and indoor tanning. Results suggested that bicultural Hispanics seek shade and wear sun protective clothing less often than Spanish-acculturated Hispanics but more often than English-acculturated Hispanics. Acculturation was not associated with sunscreen use. CONCLUSIONS Hispanic adults do not routinely engage in behaviors that reduce their risk of skin cancer. Bicultural and English-acculturated Hispanics are particularly in need of skin cancer prevention interventions.

Microfluidics Embedded Within Extracellular Matrix to Define Vascular Architectures and Pattern Diffusive Gradients Lab on a Chip. Aug, 2013 | Pubmed ID: 23787488 Gradients of diffusive molecules within 3D extracellular matrix (ECM) are essential in guiding many processes such as development, angiogenesis, and cancer. The spatial distribution of factors that guide these processes is complex, dictated by the distribution and architecture of vasculature and presence of surrounding cells, which can serve as sources or sinks of factors. To generate temporally and spatially defined soluble gradients within a 3D cell culture environment, we developed an approach to patterning microfluidically ported microchannels that pass through a 3D ECM. Micromolded networks of sacrificial conduits ensconced within an ECM gel precursor solution are dissolved following ECM gelation to yield functional microfluidic channels. The dimensions and spatial layout of channels are readily dictated using photolithographic methods, and channels are connected to external flow via a gasket that also serves to house the 3D ECM. We demonstrated sustained spatial patterning of diffusive gradients dependent on the architecture of the microfluidic network, as well as the ability to independently populate cells in either the channels or surrounding ECM, enabling the study of 3D morphogenetic processes. To highlight the utility of this approach, we generated model vascular networks by lining the channels with endothelial cells and examined how channel architecture, through its effects on diffusion patterns, can guide the location and morphology of endothelial sprouting from the channels. We show that locations of strongest gradients define positions of angiogenic sprouting, suggesting a mechanism by which angiogenesis is regulated in vivo and a potential means to spatially defining vasculature in tissue engineering applications. This flexible 3D microfluidic approach should have utility in modeling simple tissues and will aid in the screening and identification of soluble factor conditions that drive morphogenetic events such as angiogenesis.

Associations Between PBDEs in Office Air, Dust, and Surface Wipes Environment International. Jun, 2013 | Pubmed ID: 23797055 Increased use of flame-retardants in office furniture may increase exposure to PBDEs in the office environment. However, partitioning of PBDEs within the office environment is not well understood. Our objectives were to examine relationships between concurrent measures of PBDEs in office air, floor dust, and surface wipes. We collected air, dust, and surface wipe samples from 31 offices in Boston, MA. Correlation and linear regression were used to evaluate associations between variables. Geometric mean (GM) concentrations of individual BDE congeners in air and congener specific octanol-air partition coefficients (Koa) were used to predict GM concentrations in dust and surface wipes and compared to the measured concentrations. GM concentrations of PentaBDEs in office air, dust, and surface wipes were 472pg/m(3), 2411ng/g, and 77pg/cm(2), respectively. BDE209 was detected in 100% of dust samples (GM=4202ng/g), 93% of surface wipes (GM=125pg/cm(2)), and 39% of air samples. PentaBDEs in dust and air were moderately correlated with each other (r=0.60, p=0.0003), as well as with PentaBDEs in surface wipes (r=0.51, p=0.003 for both dust and air). BDE209 in dust was correlated with BDE209 in surface wipes (r=0.69, p=0.007). Building (three categories) and PentaBDEs in dust were independent predictors of PentaBDEs in both air and surface wipes, together explaining 50% (p=0.0009) and 48% (p=0.001) of the variation respectively. Predicted and measured concentrations of individual BDE congeners were highly correlated in dust (r=0.98, p

GB Virus C Infection and B-cell, Natural Killer Cell, and Monocyte Activation Markers in HIV-infected Individuals AIDS (London, England). Jul, 2013 | Pubmed ID: 23807277 GB virus C (GBV-C), a pan-lymphotropic flavivirus capable of persistent infection, is associated with prolonged survival and reduced T-cell activation in HIV-infected patients. GBV-C was associated with reduced CD56brt/CD16 natural killer cell and monocyte activation, and a trend toward reduced B-cell activation by measuring cell surface activation markers or HIV entry coreceptors. The GBV-C association was independent of HIV viral load. Thus, GBV-C may influence non-T-cell immune activation in individuals with HIV infection.

Alternative Lipid Emulsions in the Critically Ill: a Systematic Review of the Evidence Intensive Care Medicine. Jun, 2013 | Pubmed ID: 23812404 Parenteral lipid emulsions (LEs) are commonly rich in long-chain triglycerides derived from soybean oil (SO). SO-containing emulsions may promote systemic inflammation and therefore may adversely affect clinical outcomes. We hypothesized that alternative oil-based LEs (SO-sparing strategies) may improve clinical outcomes in critically ill adult patients compared to products containing SO emulsion only. The purpose of this systematic review was to evaluate the effect of parenteral SO-sparing strategies on clinical outcomes in intensive care unit (ICU) patients.

High-sensitivity Troponin: Elevated Without Infarction, is the Horse out of the Barn? Emergency Medicine Journal : EMJ. Jul, 2013 | Pubmed ID: 23825057

The Penetrance and Characteristics of Contact Lens Wear in Australia Clinical & Experimental Optometry : Journal of the Australian Optometrical Association. Jul, 2013 | Pubmed ID: 23834714 A population-based, cross-sectional telephone survey was conducted to estimate the penetrance and characteristics of contact lens wear in Australia.

An Algorithm for Generating Small RNAs Capable of Epigenetically Modulating Transcriptional Gene Silencing and Activation in Human Cells Molecular Therapy. Nucleic Acids. 2013 | Pubmed ID: 23839098 Small noncoding antisense RNAs (sasRNAs) guide epigenetic silencing complexes to target loci in human cells and modulate gene transcription. When these targeted loci are situated within a promoter, long-term, stable epigenetic silencing of transcription can occur. Recent studies suggest that there exists an endogenous form of such epigenetic regulation in human cells involving long noncoding RNAs. In this article, we present and validate an algorithm for the generation of highly effective sasRNAs that can mimic the endogenous noncoding RNAs involved in the epigenetic regulation of gene expression. We validate this algorithm by targeting several oncogenes including AKT-1, c-MYC, K-RAS, and H-RAS. We also target a long antisense RNA that mediates the epigenetic repression of the tumor suppressor gene DUSP6, silenced in pancreatic cancer. An algorithm that can efficiently design small noncoding RNAs for the epigenetic transcriptional silencing or activation of specific genes has potential therapeutic and experimental applications.Molecular Therapy-Nucleic Acids (2013) 2, e104; doi:10.1038/mtna.2013.33; published online 9 July 2013.

Randomized Trial of NRT, Bupropion, and NRT Plus Bupropion for Smoking Cessation: Effectiveness in Clinical Practice Addiction (Abingdon, England). Jul, 2013 | Pubmed ID: 23859696 Bupropion was introduced for smoking cessation following a pivotal trial showing that it gave improved efficacy over the nicotine patch and also suggesting combination treatment was beneficial. We tested in clinical practice for an effectiveness difference between bupropion and nicotine replacement therapy (NRT), whether the combination improves effectiveness, and whether either treatment might be more beneficial for certain sub-groups of smokers.

Concerns Regarding Results of a Randomized Controlled Trial to Promote Skin Self-examination and Sun Protection Behaviors JAMA Dermatology (Chicago, Ill.). Jul, 2013 | Pubmed ID: 23864093

Quantification of Mitochondrial Acetylation Dynamics Highlights Prominent Sites of Metabolic Regulation The Journal of Biological Chemistry. Jul, 2013 | Pubmed ID: 23864654 Lysine acetylation is rapidly becoming established as a key post-translational modification (PTM) for regulating mitochondrial metabolism. Nonetheless, distinguishing regulatory sites from among the thousands identified by mass spectrometry and elucidating how these modifications alter enzyme function remain primary challenges. Here, we performed multiplexed quantitative mass spectrometry to measure changes to the mouse liver mitochondrial acetyl-proteome in response to acute and chronic alterations in nutritional status, and integrated these data sets with our compendium of predicted Sirt3 targets. These analyses highlight a subset of mitochondrial proteins with dynamic acetylation sites, including acetyl-CoA acetyltransferase 1 (Acat1) - an enzyme central to multiple metabolic pathways. We performed in vitro biochemistry and molecular modeling to demonstrate that acetylation of Acat1 decreases its activity by disrupting the binding of Coenzyme A. Collectively, our data reveal an important new target of regulatory acetylation, and provide a foundation for investigating the role of select mitochondrial protein acetylation sites in mediating acute and chronic metabolic transitions.

Treatment of Intracranial Aneurysms with the Pipeline Embolization Device from a U.S. Multicenter Experience World Neurosurgery. Jul, 2013 | Pubmed ID: 23871814

Ca2+ Release-activated Ca2+ Channel Blockade As a Potential Tool in Antipancreatitis Therapy Proceedings of the National Academy of Sciences of the United States of America. Jul, 2013 | Pubmed ID: 23878235 Alcohol-related acute pancreatitis can be mediated by a combination of alcohol and fatty acids (fatty acid ethyl esters) and is initiated by a sustained elevation of the Ca(2+) concentration inside pancreatic acinar cells ([Ca(2+)]i), due to excessive release of Ca(2+) stored inside the cells followed by Ca(2+) entry from the interstitial fluid. The sustained [Ca(2+)]i elevation activates intracellular digestive proenzymes resulting in necrosis and inflammation. We tested the hypothesis that pharmacological blockade of store-operated or Ca(2+) release-activated Ca(2+) channels (CRAC) would prevent sustained elevation of [Ca(2+)]i and therefore protease activation and necrosis. In isolated mouse pancreatic acinar cells, CRAC channels were activated by blocking Ca(2+) ATPase pumps in the endoplasmic reticulum with thapsigargin in the absence of external Ca(2+). Ca(2+) entry then occurred upon admission of Ca(2+) to the extracellular solution. The CRAC channel blocker developed by GlaxoSmithKline, GSK-7975A, inhibited store-operated Ca(2+) entry in a concentration-dependent manner within the range of 1 to 50 Î¼M (IC50 = 3.4 Î¼M), but had little or no effect on the physiological Ca(2+) spiking evoked by acetylcholine or cholecystokinin. Palmitoleic acid ethyl ester (100 Î¼M), an important mediator of alcohol-related pancreatitis, evoked a sustained elevation of [Ca(2+)]i, which was markedly reduced by CRAC blockade. Importantly, the palmitoleic acid ethyl ester-induced trypsin and protease activity as well as necrosis were almost abolished by blocking CRAC channels. There is currently no specific treatment of pancreatitis, but our data show that pharmacological CRAC blockade is highly effective against toxic [Ca(2+)]i elevation, necrosis, and trypsin/protease activity and therefore has potential to effectively treat pancreatitis.

Health Inequalities and Regional Specific Scarcity in Primary Care Physicians: Ethical Issues and Criteria International Journal of Public Health. Jul, 2013 | Pubmed ID: 23880912 A substantial body of evidence supports the beneficial health impact of an increase in primary care physicians for underserved populations. However, given that in many countries primary care physician shortages persist, what options are available to distribute physicians and how can these be seen from an ethical perspective?

Whole-body Heat Loss is Reduced in Older Males During Short Bouts of Intermittent Exercise American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. Jul, 2013 | Pubmed ID: 23883671 Studies in young adults show that a greater proportion of heat is gained shortly following the start of exercise and that temporal changes in whole-body heat loss during intermittent exercise have a pronounced effect on body heat storage. The consequences of short duration intermittent exercise on heat storage with aging are unclear. We compared evaporative heat loss (HE) and changes in body heat content (Î”Hb) between young (20-30 years), middle-age (40-45 years) and older males (60-70 years) of similar body mass and surface area, during successive exercise (4x15-min) and recovery periods (4x15-min) at a fixed rate of heat production (400W) and under fixed environmental conditions (35Â°C/20% relative humidity). HE was lower in older males versus young males during each exercise (Ex1: 283Â±10 vs. 332Â±11 kJ, Ex2: 334Â±10 vs. 379Â±5 kJ, Ex3: 347Â±11 vs. 392Â±5 kJ, Ex4: 347Â±10 vs. 387Â±5 kJ, all P

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In JoVE (1)

Other Publications (199)

Articles by Eloise Stapleton in JoVE

Biology

Other articles by Eloise Stapleton on PubMed

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